Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0001430 (adenoma)
21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The i.p. injection of caffeine (8, 20, and 40 mg/kg) 3 times weekly for 8 weeks suppressed the development of spontaneous pulmonary adenomas in strain A mice. The same caffeine injection scheme suppressed urethan (0.25 and 1.0 mg/g)-induced lung tumor development when caffeine treatment started 1 week before urethan administration, but this suppression was not significant when caffeine treatment was initiated 1 week after urethan injection. The most pronounced suppression of lung tumor formation occurred when caffeine was given as only two injections 3 hr before and 3 hr after urethan administration. The incorporation of [3H]thymidine into lung tissue DNA of caffeine-treated mice was impaired at the time of urethan administration. Also, caffeine partially antagonized the effects of urethan on lung tissue, as measured by [3H]thymidine incorporation studies. One interpretation of these results is that caffeine-induced suppression of DNA synthesis interferes with pulmonary adenoma induction by decreasing the affinity of lung tissue DNA for urethan. The finding that chronic caffeine treatment produced continued suppression of [3H]thymidine incorporation into lung tissue DNA suggests that caffeine-induced inhibition of spontaneous pulmonary adenoma formation is due to a general suppression of lung DNA-synthetic activity.
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PMID:Inhibiting effect of caffeine on spontaneous and urethan-induced lung tumors in strain A mice. 64 85

Lung adenomas were induced in strain A mice by chronic treatment with N-nitroso compounds (given in drinking water) and with amines or ureas in food plus NaNO2 in drinking water. We studied the effects of varying the concentrations of three N-nitroso compounds and NaNO2 concentration in the morpholine plus NaNO2 and methylurea plus NaNO2 systems. Sodium ascorbate (NaASC) at the highest level tested (11.5 or 23 g/kg food) gave 89-98% inhibition of adenoma induction by the NaNO2 plus piperazine, morpholine, and methylurea systems. In 7 groups, NaASC produced increases of 15-59% in adenoma induction by nitrosomorpholine (NM) and mononitrosopiperazine (MNP), possibly because the mice consumed more of the nitrosamine solution. Adenoma induction by morpholine plus NaNO2 was strongly inhibited by gallic acid, moderately inhibited by caffeine, and unaffected by thiocyanate (all added to the food). Gallic acid inhibited or had no effect on the action of NM and MNP. We discussed the proposal that NaASC (or perhaps gallic acid) be administered with readily nitrosatable drugs.
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PMID:Induction of mouse lung adenomas by amines or ureas plus nitrite and by N-nitroso compounds: effect of ascorbate, gallic acid, thiocyanate, and caffeine. 115 40

Various long-term bioassay methods have been used to determine the carcinogenicity of chemical substances. Among them, a long-term method developed by Toth (1968), which scores the incidence of pulmonary adenoma formation at 28 to 56 weeks following subcutaneous administration of chemical carcinogens to new-born mice is used widely. This particular long-term bioassay method, while it takes long periods, has proved useful in determining the anticarcinogenic effect of ginseng extracts against the pulmonary adenoma formation inducible with dimethylbenzanthracene, urethane, and aflatoxin B1. More recently, in order to shorten the assay durations to 9 weeks (medium-term), we have modified the existing method by adjusting the doses of carcinogens to be administered to the new-born mice. We have established a modified method in which 40-50% of mice were found to develop pulmonary adenoma 9 weeks after a subcutaneous injection of 0.5 mg/kg to new-born mice of NIH(GP) strain and this modified medium-term bioassay system was found useful in the screening of cancer preventive agents among natural products, such as ginseng and caffeine.
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PMID:Usefulness of medium-term bioassay determining formations of pulmonary adenoma in NIH(GP) mice for finding anticarcinogenic agents from natural products. 192 May 44

A single large dose of caffeine (100 microgram/g body weight) was injected at different time in relation to urethan initiation for skin tumorigenesis, topical anthranil treatment serving as promotor. Caffeine significantly increased papilloma incidence when given 6 h before initiation, and to an insignificant extent, at 9 h prior to initiation. A tendency for inhibition was evident when caffeine was administered 6 h after urethan but this was also not statistically significant. Lung adenoma induction by urethan was unaffected. The significance of the timing of caffeine treatment in modifying the outcome of the initiation phase is discussed.
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PMID:The effect of caffeine on two-stage skin carcinogenesis and on complete systemic carcinogenesis. 729 65

A new medium-term in vivo model was tried using pulmonary adenoma induced by benzo(a)pyrene (BP) in newborn mice. Both inbred mice such as C57BL/5J, C57BR/cdJ. A/J mice and non inbred N:GP(S) mice were used. Benzo(a)pyrene was injected in the subscapular region of newborn mice within 24 hours after birth at a dose of 0.5 mg and 1 mg per mouse, respectively. After 9 weeks lung tumor induced in N:GP(S) and A/J mice but in the other mice. The dose showing a 50% tumor incidence was found in N:GP(S) mice to be 0.5 mg of BP but the tumor incidence was very high in A/J mice even at 40 micrograms of BP, the lowest dose in this experiment. To verify the utility of this model, ascorbic acid, carrot, beta carotene, soybean lecithin, spinach, Sesamum indicum, Ganoderma lucidum, caffeine, red ginseng extract, fresh ginseng and 13-cis retinoic acid, some of which are known to have anticarcinogenic activity in various animal models, were tried with this system. Ascorbic acid, soybean lecithin, Ganoderma lucidum, caffeine and red ginseng extract showed inhibition of lung tumor incidence, while fresh ginseng, carrot, beta carotene, spinach and 13-cis retinoic acid did not. This result suggested that the 9-week medium-term model using lung tumor induced by 0.5 mg of BP was useful for the screening of cancer preventive agents.
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PMID:Trial of a new medium-term model using benzo(a)pyrene induced lung tumor in newborn mice. 764 68

We have previously identified a p53-independent apoptotic response that is delayed until 48-72 h after irradiation of colorectal adenoma and carcinoma cells. Because the delay appears to be in part due to a transient G2 cell cycle arrest, the importance of this checkpoint in the mechanism of ionizing radiation (IR)-induced death of colorectal tumor cells was investigated. An adenoma cell line with (282Arg-->Trp) mutant p53 (S/RG/C2) and a carcinoma cell line (PC/JW/FI) lacking p53 protein treated with 5 Gy IR in the presence of 1.5 mm caffeine (CAF) reduced IR-induced G2 arrest and increased the level of apoptosis (1.5-1.6-fold) 24 h after treatment. Increased IR apoptotic cell death with CAF significantly reduced IR cell survival over a 7-day period in S/RG/C2 and PC/JW/FI. To investigate whether CAF radiosensitization correlated with lack of wild-type (wt) p53, we studied transfected derivatives of an adenoma-derived cell line (PC/AA/C1), in which the endogenous wt p53 activity was disrupted by the expression of a dominant negative (273Arg-->His) p53 mutant protein (designated AA/273p53/B). This p53-defective cell line was also radiosensitized by CAF, whereas the vector control (AA/PCMV/D), which retained wt p53 activity, was not. In addition, as with the S/RG/C2 and PC/JW/FI cell lines, the 7-day IR cell survival was reduced significantly in AA/273p53/B compared with the vector control cell line. This suggests that radiosensitization by CAF and increased cell death is dependent on loss of wt p53 function. Interestingly, radiosensitization of the AA/273p53/B cell line was not associated with accelerated apoptosis but correlated with increased polyploid giant cells, which have been associated with disruption of cell cycle checkpoints and genomic instability. These results demonstrate that G2 checkpoint inhibition with CAF leads to preferential IR cell killing in cell lines in which wt p53 is inactivated and that this increased cell killing is not necessarily dependent on increased IR-induced apoptosis.
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PMID:Inhibition of radiation-induced G2 delay potentiates cell death by apoptosis and/or the induction of giant cells in colorectal tumor cells with disrupted p53 function. 981 21

High red meat intake has been linked with an increased risk of colorectal cancer and adenomas. During high temperature cooking of red meats, heterocyclic amines (HCAs) are generated; however, to be carcinogenic, they must be metabolized by enzymes including cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 (NAT1) and/or N-acetyltransferase 2 (NAT2). We have conducted a clinic-based case-control study of colorectal adenomas that focused on assessment of exposure to HCAs (estimated by use of a HCA database and meat cooking module) and modification of these exposures by genetic factors. We have previously reported that intake of MeIQx was associated with an increased risk of colorectal adenomas [overall association at 80th percentile, > 27.00 ng/day: odds ratio (OR) = 2.68, 95% confidence interval (CI) 1.58-4.55]. Here, we report our evaluation of whether variation in CYP1A2, NAT1 and/or NAT2 modify the association between HCAs and colorectal adenoma formation in 146 cases and 228 frequency-matched controls. The NAT1*10 allele was associated with a nonsignificant increased risk of colorectal adenomas (OR = 1.43; 95% CI 0.86-2.36). Further, when we analysed 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake as a categorical variable, we observed a six-fold increase in adenoma risk among rapid NAT1 acetylators who consumed more than 27 ng a day (OR = 6.50; 95% CI 2.16-19.7), whereas among slow NAT1 acetylators, the increase in risk was two-fold (OR = 2.32; 95% CI 1.12-4.81). While suggestive, the results were not significantly different from each other on either an additive or multiplicative scale. In contrast, NAT2 genotype and CYP1A2 and NAT2 hepatic activity measured by caffeine urinary metabolites were not associated with adenoma risk, although an increase in risk with rapid CYP1A2 activity could not be ruled out (OR = 1.46; 95% CI 0.76-2.81). Moreover, there was no evidence that the effect of MeIQx was enhanced among subjects in any subgroup defined by variation in these measures. These results are compatible with the hypothesis that high HCA exposure is associated with an increased risk of colorectal adenomas, particularly in genetically susceptible subgroups. Further study of larger populations is needed to confirm and extend these observations.
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PMID:Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas. 1187 68

Theophylline is an alkaloid found in tea (Thea sinensis) and chocolate and is structurally related to caffeine and theobromine. Theophylline is used as a pharmaceutical agent. It stimulates the heart and central nervous system, relaxes the smooth muscles of the bronchi and blood vessels, and causes diuresis. The drug is used mainly as a bronchodilator in obstructive airway diseases, such as bronchial asthma, and for myocardial stimulation. Theophylline was nominated for toxicologic and carcinogenicity testing as a representative of the purine structural subclass, particularly because of its relationship to purines such as caffeine, 1-methyl-3-hydroxyguanine, and 3-hydroxy-1-methylxanthine, the latter two compounds having been shown to induce sarcomas in rats. Additional reasons for testing theophylline included its widespread use in humans as a pharmaceutical agent, its possible genotoxicity in vitro, and the lack of information on its potential toxicity and/or carcinogenicity under conditions of chronic oral usage. Based on reported teratogenicity and testicular toxicity, it was also recommended that reproductive studies be included in the evaluation of theophylline. The oral route of administration was selected because it is the primary route of human exposure, and the gavage route was selected because it mimics the pharmaceutical use of theophylline in humans. Male and female F344/N rats and B6C3F1 mice were given theophylline (greater than 99% pure) in feed or in corn oil by gavage for 16 days or 14 weeks or in corn oil by gavage for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, mouse bone marrow, and mouse peripheral blood. 16-DAY FEED STUDY IN RATS: Groups of five male and five female F344/N rats were given 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm theophylline in feed for 16 days, which resulted in approximate daily doses of 50, 100, 250, 450, or 1,000 mg theophylline/kg body weight to males and 75, 150, 250, 450, or 1,100 mg/kg to females. All rats survived until the end of the study. The final mean body weights and body weight gains of 8,000 ppm males and females were significantly less than those of the controls. The absolute and relative testis weights of 4,000 ppm males were significantly greater than those of the controls. Increased incidences of uterine hypoplasia were observed microscopically in exposed groups of females. 16-DAY GAVAGE STUDY IN RATS: Groups of five male and five female F344/N rats were given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), or 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. All rats receiving 400 mg/kg once daily and all but one female receiving 200 mg/kg twice daily died during the study. In groups dosed once daily, final mean body weights and body weight gains of males receiving 100 or 200 mg/kg and mean body weight gains of females receiving 50, 100, or 200 mg/kg were less than those of controls. The final mean body weights and body weight gains of groups receiving theophylline twice daily were generally similar to those of groups receiving the same daily dosages once daily. Clinical findings included rapid or labored respiration, hunched posture, and squinting. In groups dosed once daily, absolute and relative uterus weights of females receiving 100 or 200 mg/kg once daily were significantly less than those of the controls, and the absolute and relative uterus weights of females receiving 100 mg/kg once daily were significantly less than those of females receiving 50 mg/kg twice daily. Uterine atrophy was observed in three females receiving 200 mg/kg twice daily. Periarteritis of the mesenteric arteries was observed in two males and two females receiving 400 mg/kg once daily. 16-DAY FEED STUDY IN MICE: Groups of five male and five female B6C3F1 mice were given 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm theophylline in feed for 16 days, resulting in approximate daily doses of 250, 475, 950, 1,800, or800, or 2,000 mg theophylline/kg body weight to males and 300, 450, 1,225, 2,000, or 4,375 mg/kg to females. All mice survived until the end of the study. Final mean body weights of 4,000 and 8,000 ppm females and mean body weight gains of 2,000, 4,000, and 8,000 ppm females were significantly greater than those of the controls. Feed consumption by exposed groups was similar to that by the controls, except that by the 8,000 ppm males, which was approximately 40% the amount of feed consumed by the control group. Histopathologic examinations were not performed due to the absence of mortality and significant exposure-related lesions. 16-DAY GAVAGE STUDY IN MICE: Groups of five male and five female B6C3F1 mice were given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), or 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. Three males and all females receiving 400 mg/kg once daily died on day 1. There were no significant differences in final mean body weights or body weight gains. There were no histopathologic findings attributed directly to theophylline. 14-WEEK FEED STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were given 0, 1,000, 2,000, or 4,000 ppm theophylline in feed for 14 weeks, which resulted in approximate daily doses of 75, 125, or 250 mg theophylline/kg body weight to males and 75, 125, or 275 mg/kg to females. The final mean body weight of 1,000 ppm females was significantly greater than that of the control group. Feed consumption by exposed groups was similar to that by the controls. Mean cell volume and mean cell hemoglobin were significantly greater in males exposed to 2,000 or 4,000 ppm than those in the control group. Segmented neutrophil counts of all groups of exposed females were significantly greater than that of the control group. The absolute and relative kidney weights of 4,000 ppm males were significantly greater than those of the controls, and there was an exposure-related increase in the severity of nephropathy in males. Exposure-related increases in the incidences of mesenteric and/or pancreatic periarteritis were observed in males and females. 14-WEEK GAVAGE STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were given 0, 37.5, 75, or 150 mg theophylline/kg body weight in corn oil by gavage for 14 weeks. One male and one female receiving 150 mg/kg died before the end of the study. The mean body weight gain of 150 mg/kg females was significantly greater than that of the controls. Mean cell volume of 150 mg/kg males and mean cell hemoglobin of all groups of dosed males were significantly greater than those of the control group. There were slight dose-dependent increases in the incidences of mesenteric periarteritis in dosed males and females. 14-WEEK FEED STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were given 0, 1,000, 2,000, or 4,000 ppm theophylline in feed for 14 weeks, resulting in approximate daily doses of 175, 400, or 800 mg theophylline/kg body weight to males and 225, 425, or 850 mg/kg to females. All mice survived until the end of the study. The final mean body weights and body weight gains of all exposed groups of males and females were significantly less than those of the controls. Feed consumption by exposed groups was similar to that by the controls. Leukocyte, segmented neutrophil, and lymphocyte counts of 4,000 ppm males were significantly greater than those of the controls. Leukocyte and segmented neutrophil counts of 2,000 or 4,000 ppm females were significantly greater than those of the controls. There were no histopathologic findings attributed directly to theophylline exposure. 14-WEEK GAVAGE STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were given 0, 75, 150, or 300 mg theophylline/kg body weight in corn oil by gavage for 14 weeks. Three males and all females receiving 300 mg/kg, one 75 mg/kg male, and one control female died before the end of the study. Final mean body weights and body weight gains of 150 and 300 mg/kg males were significantly less than those of the controls. Mean cell volume and mean cell hemoglobin of 300 mg/kg males were significantly greater than those of the controls. There were no histopathologic findings attributed directly to theophylline treatment. 2-YEAR GAVAGE STUDY IN RATS: Groups of 50 male and 50 female rats were given 7.5, 25, or 75 mg theophylline/kg body weight in corn oil by gavage for 2 years. Survival and Body Weights: There were no significant differences in survival between dosed and control groups. Final mean body weights of all groups of dosed males and females were significantly less than those of the controls. Pathology Findings: There were no significantly increased incidences of neoplasms in dosed rats. The incidence of chronic inflammation of the mesenteric arteries was significantly increased in males receiving 75 mg/kg compared to the controls. There were doserelated negative trends in the incidences of mammary gland fibroadenoma and fibroadenoma or carcinoma (combined) in females; these differences correlated with decreased body weights. 2-YEAR GAVAGE STUDY IN MICE: Groups of 50 male B6C3F1 mice were given 0, 15, 50, or 150 mg theophylline/kg body weight and groups of 50 female B6C3F1 mice were given 0, 7.5, 25, or 75 mg/kg in corn oil by gavage for 2 years. Survival and Body Weights: Survival of 150 mg/kg males was significantly less than that of the controls. The final mean body weights of 150 mg/kg males, 25 mg/kg females, and 75 mg/kg females were significantly less than those of the control groups. Pathology Findings: There were no treatment-related increases in incidences of nonneoplastic lesions or neoplasms. In males and females, there were decreased incidences of hepatocellular adenoma and of the combined incidences of hepatocellular adenoma or carcinoma compared to the controls. Male mice had a pattern of nonneoplastic liver lesions along with silver-staining helical organisms in the liver consistent with Helicobacter hepaticus infection. The incidences of these liver lesions in 150 mg/kg males were significantly lower than those in control males. Increases in the incidences of hepatocellular neoplasms in male mice have been shown to be associated with H. hepaticus infection when hepatitis is also present. Because of this association, interpretation of the decreased incidence of liver neoplasms in male mice was more difficult. Incidences of lesions at other sites in this study were not considered to have been significantly impacted by H. hepaticus infection or its associated hepatitis. GENETIC TOXICOLOGY: Theophylline was not mutagenic in Salmonella typhimurium, with or without metabolic activation (S9). It induced sister chromatid exchanges but not chromosomal aberrations in cultured Chinese hamster ovary cells. The positive sister chromatid exchange response was noted only in the absence of S9. In vivo, a mouse bone marrow sister chromatid exchange test showed positive results at a standard 23-hour harvest time; however, this test was not repeated and the response is unconfirmed. An in vivo mouse bone marrow chromosomal aberrations test, that employed both standard and extended exposure protocols, gave negative results. The frequency of micronucleated erythrocytes was determined in peripheral blood of male and female mice exposed to theophylline in dosed feed or in corn oil by gavage for 14 weeks. No significant increases in the frequencies of micronucleated cells were seen in male or female mice in either of the studies. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of theophylline in male or female F344/N rats administered 7.5, 25, or 75 mg/kg. There was no evidence of carcinogenic activity of theophylline in male B6C3F1 mice administered 15, 50, or 150 mg/kg or female B6C3F1 mice administered 7.5, 25, or 75 mg/kg. Gavage administration of theophylline caused chronic inflammation of the mesenteric arteries in dosed male rats. Decreased incidences of mammary neoplasms in female rats were likely associated with lower body weights. There were dose-related decreases in the incidences of hepatocellular adenoma and hepatocellular carcinoma in male and female mice. Synonyms: 3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione; 1,3-dimethylxanthine; 1H-purine-2,6-dione; NSC 2066; pseusdotheophylline; theocin; theophyllin; theophylline, anhydrous Trade names: Accurbron; Aerobin; Aerolate III; Afonilum; Aminophylline; Aquaphyllin; Armophylline; Asmalix; Bilordyl; Bronchoretard; Bronkodyl; Cetraphylline; Constant-T; Diffumal; Duraphyl; Duraphyllin; Elixicon; Elixophyllin; Euphylline L.A.; Euphylong; LaBID; Labophylline; Lanophyllin; Lasma; Liquophylline; Optiphyllin; Parkophyllin; Phylocontin; Physpan; Pro-Vent; PulmiDur; Pulmo-Timelets; Quibron; Respbid; Rona-Phyllin; Sabidal; Slo-bid; Slo-Phyllin; Solosin; Sustaire; Tefamin; Teobid; Teofyllamin; Tesona; Theal tablets; Theo-24; Theobid; Theocap; Theochron; Theoclear; Theocontin; Theo-Dur; Theofol; Theograd; Theolair; Theolan; Theolix; Theophyl; Theoplus; Theo-Sav; Theosol; Theospan; Theostat; Theovent; TheoX; T-Phyl; Truphylline; Uni-Dur; Unifyl; Uniphyl; Uniphyllin; Xanthium
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PMID:NTP Toxicology and Carcinogenesis Studies of Theophylline (CAS No. 58-55-9) in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies). 1257 77

Tea and tea constituents have been shown by different investigators to inhibit lung tumorigenesis in different animal model systems. This includes lung tumorigenesis in A/J mice induced by 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK), N-nitrosodiethylamine, benzo[a]pyrene, N-nitrosomethylurea, or cisplatin. Inhibition of lung tumorigenesis has also been demonstrated in C3H mice treated with N-nitrosodiethylamine. In most of these experiments, reduction in tumor number and tumor size has been observed in the tea-treated group, and in some experiments, decreased tumor incidence has also been observed. The green tea constituent, epigallocatechin-3-gallate (EGCG), and the black tea constituent, theaflavins, have also been shown to be effective. Black tea preparations have been shown to reduce the incidence and number of spontaneously generated lung adenocarcinomas and rhabdomyosarcoma in A/J mice, as well as inhibit the progression of lung adenoma to adenocarcinoma. The mechanisms for the inhibitory action have not been well elucidated. It may be related to the antiproliferative, proapoptotic, and antiangiogenic activities of tea constituents that have been demonstrated in some experiments. These activities may be a result of the inhibition of key protein kinases involved in signal transduction and cell cycle regulation. Tea catechins, such as EGCG, have been suggested to be the effective components. However, a study suggests that caffeine is the key effective constituent for the inhibitory activity of lung tumorigenesis in Fisher 344 rats by black tea. In many of the experiments, tea consumption resulted in the reduction of body fat and body weight; these factors may also contribute to the inhibition of tumorigenesis.
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PMID:Inhibition of lung tumorigenesis by tea. 1576 23

The present study investigated the inhibitory effects of Polyphenon E [a standardized green tea polyphenol preparation containing 65% (-)-epigallocatechin-3-gallate] and caffeine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6- and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation.
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PMID:Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine. 1714 98


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