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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The modifying effects of dietary feeding of bovine lactoferrin (bLF) on tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR), polyamine content and ornithine decarboxylase (ODC) activity in the tongue were also examined for mechanistic analysis of possible modifying effects of bLF on carcinogenesis. At 7 weeks of age, all animals except those treated with bLF alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 7 days before 4-NQO exposure, experimental groups were fed experimental diets containing bLF (0.2% and 2%) for 10 weeks ("initiation feeding"). Starting 1 week after the cessation of exposure to 4-NQO, the other experimental groups given 4-NQO and a basal diet were fed the experimental diets for 22 weeks ("postinitiation feeding"). At week 32, the incidence and multiplicity of tongue neoplasms in the "initiation feeding" groups of 0.2% and 2% bLF and the "post-initiation feeding" group of 0.2% bLF were lower than those of the 4-NQO alone group, but without statistical significance. However, "post-initiation feeding" of 2% bLF caused a significant reduction in the incidence (20% vs. 55%, P=0.02418) and multiplicity (0.25+/-0.54 vs. 0.70+/-0.71, P<0.05) of tongue squamous cell carcinoma (by 64%, P=0.02418). bLF treatment elevated liver and tongue GST activities and liver QR activity. The "post-initiation feeding" with 2% bLF significantly decreased QR activity, proliferating cell nulcear antigen-positive index and ODC activity in the tongue. In addition, feeding with bLF decreased tongue polyamine content. These results suggest that bLF, when given at the 2% dose level during the post-initiation phase, exerts chemopreventive action against tongue tumorigenesis through modification of cell proliferation activity and/or the activities of detoxifying enzymes.
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PMID:Chemopreventive effect of bovine lactoferrin on 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. 1074 41

Numerous phytochemicals have been examined for their capacity to act as cancer chemopreventive agents. Dibenzoylmethane, a minor constituent of licorice and a compound structurally-related to curcumin, recently was identified as an effective inhibitor of chemically-induced rat mammary DNA-adduct formation and tumorigenesis (Carcinogenesis 19(1998)1039-1043). The present studies were conducted to examine the capacity of dibenzoylmethane to inhibit the formation of DNA adducts following exposure to benzo[a]pyrene (BP) and 1,6-dinitropyrene (1,6-DNP), and to stimulate the expression of glutathione-S-transferase (GST) and NAD(P)H-quinone reductase (QR) proteins in the human mammary epithelial cell line MCF-10F. In addition, the efficacy of dibenzoylmethane as an enzyme inducer and adduct inhibitor was compared with that of sulforaphane, a potent inducer of phase II detoxification enzymes and inhibitor of chemically-induced rat mammary tumorigenesis. Dibenzoylmethane at concentrations from 0.1 M to 2.0 microM inhibited BP-DNA adduct formation by 63 to 81%. Likewise, sulforaphane inhibited BP-DNA adduct formation by 68 to 80% over the same concentration range. DNA adduct formation following exposure to 1,6-DNP was significantly inhibited by 46 to 61% due to dibenzoylmethane treatment (0.1 to 2.0 microM) and 30 to 56% due to sulforaphane treatment at the same concentrations. The expression of QR and GSTP1-1 proteins were increased by 3 to 4-fold and 3 to 5-fold, respectively, for MCF-10F cells treated with sulforaphane (0.5-2.0 microM). Dibenzoylmethane treatment at the same concentrations did not induce GSTP1-1 expression and significantly stimulated QR expression only at the 2.0 microM concentration. These data indicate that human mammary epithelial MCF-10F cells can convert BP and 1,6-DNP to DNA-binding forms, and that DNA adduct formation can be inhibited by the phytochemicals dibenzoylmethane and sulforaphane. The inhibition of BP-DNA and 1, 6-DNP adduct formation by sulforaphane was associated with increases in QR and GST protein expression. The mechanisms underlying the capacity of dibenzoylmethane to inhibit BP-DNA and 1,6-DNP-DNA adduct formation could not be explained by changes in QR or GST expression and remain to be determined. Together these data suggest that dibenzoylmethane and sulforaphane warrant continued evaluation as breast cancer chemopreventive agents.
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PMID:Inhibition of benzo[a]pyrene- and 1,6-dinitropyrene-DNA adduct formation in human mammary epithelial cells bydibenzoylmethane and sulforaphane. 1081 78

Isothiocyanates (ITCs) are abundant in the human diet. Many potently inhibit tumorigenesis induced by a wide variety of chemical carcinogens in rodents. Recently, we observed that several ITCs accumulated to very high concentrations in cultured cells and that their accumulated levels were closely related to their potencies in inducing phase II enzymes [NAD(P)H:quinone reductase and glutathione transferases] that detoxify carcinogens. To elucidate the molecular mechanism responsible for this accumulation, the intracellular chemical identities of two ITCs, sulforaphane [SF, 1-isothiocyanato-(4R,S)-(methylsulfinyl)butane] and benzyl-ITC, were investigated in murine hepatoma cells. Both ITCs accumulated very rapidly to high intracellular concentrations, but, remarkably, most of the intracellular forms of the ITCs were dithiocarbamates resulting from conjugation with reduced glutathione (GSH). For example, the intracellular concentration reached 6.4 mM when cells were exposed to 100 microM SF for 30 min at 37 degrees C and 95% of the accumulated product was the GSH conjugate. Cellular accumulation of each ITC was accompanied by a profound reduction in cellular GSH levels. These findings, together with our previous observation that accumulation of ITCs depended on cellular GSH levels, strongly suggest that intracellular conjugation of ITCs with GSH is mainly responsible for ITC accumulation. Surprisingly, rapid accumulation to high concentrations also occurred when cells were exposed to the GSH-ITC conjugates. However, these conjugates were apparently not absorbed intact, but were hydrolyzed extracellularly to free ITCs that were taken up by the cells. This conclusion is supported by the finding that suppression of dissociation of the conjugates by excess GSH or other thiols blocks accumulation of the conjugates.
Carcinogenesis 2000 Jun
PMID:Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells. 1083 7

The modifying effects of dietary feeding of a polyisoprenylated benzophenone, garcinol, isolated from Garcinia indica fruit rind on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of garcinol on proliferating cell nuclear antigen (PCNA) index in ACF and activities of detoxifying enzymes of glutathione S-transferase (GST) and quinone reductase (QR) in liver. In addition, we examined the effects of garcinol on 12-O-tetradecanoylphorbol-13-acetate-induced O(2)(-) generation in differentiated human promyelocytic HL-60 cells and lipopolysaccharide (LPS)- and interferon (IFN)-gamma-induced nitric oxide (NO) generation in mouse macrophage RAW 264.7 cells. Western blotting analysis of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression was done in LPS- and IFN-gamma-treated mouse macrophage RAW 264.7 cells. Rats were given subcutaneous injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce ACF. They also received the experimental diet containing 0.01 or 0.05% garcinol for 5 weeks, starting 1 week before the first dosing of AOM. AOM exposure produced 97 +/- 15 ACF/rat at the end of the study (week 5). Dietary administration of garcinol caused significant reduction in the frequency of ACF: 72 +/- 15 (26% reduction, P < 0.01) at a dose of 0.01% and 58 +/- 8 (40% reduction, P < 0.001) at a dose of 0.05%. Garcinol administration significantly lowered PCNA index in ACF. Feeding of garcinol significantly elevated liver GST and QR activities. In addition, garcinol could suppress O(2)(-) and NO generation and expression of iNOS and COX-2 proteins. These findings might suggest possible chemopreventive ability of garcinol, through induction of liver GST and QR, inhibition of O(2)(-) and NO generation and/or suppression of iNOS and COX-2 expression, on colon tumorigenesis.
Carcinogenesis 2000 Jun
PMID:Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats. 1083 8

The modifying effects of dietary administration of ferulic acid (FA) on azoxymethane (AOM)-induced colon carcinogenesis were examined in three experiments with male 344 rats. In the first experiment, the modifying effect of FA on AOM (15 mg/kg body weight, once a week, for 3 weeks)-induced formation of aberrant crypt foci (ACF) was examined in five groups. Numbers of ACF/colon of groups 2 (AOM+250 ppm FA) and 3 (AOM+500 ppm FA) at the termination (5 weeks after the start) were smaller than of group 1 (AOM alone). Those of ACF/cm(2) of group 3 were also smaller than of group 1 (P<0.05). In the second experiment, a long-term assay for the effects of FA was conducted with seven groups. At the termination (35 weeks), groups 2 and 3 which were given FA during the initiation phase at doses of 250 and 500 ppm, respectively, had lower incidences of colonic carcinomas (23 and 27%, respectively) than group 1 which was given AOM alone (59%; P<0.05). In the third experiment, to determine whether FA could modify the activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR) in liver and colon, 60 rats were gavaged with FA at four doses (0, 25, 50, 100 mg/kg body weight). Dosing of 100 mg/kg significantly elevated GST activity in liver (P<0.03), and QR activities in liver and colonic mucosa (P<0.01 and P<0.02, respectively), suggesting that detoxifying enzymes are related to the blocking effect of FA on AOM-induced colon carcinogenesis.
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PMID:Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats. 1089 37

Watercress is an exceptionally rich dietary source of beta-phenylethyl isothiocyanate (PEITC). This compound inhibits phase I enzymes, which are responsible for the activation of many carcinogens in animals, and induces phase II enzymes, which are associated with enhanced excretion of carcinogens. In this study, we show that watercress extracts are potent inducers of quinone reductase (QR) in murine hepatoma Hepa 1c1c7 cells, a widely adopted assay for measuring phase II enzyme induction. However, contrary to expectations, this induction was not associated with PEITC (which is rapidly lost to the atmosphere upon tissue disruption due to its volatility) or a naturally occurring PEITC-glutathione conjugate, but with 7-methylsulfinyheptyl and 8-methylsulfinyloctyl isothiocyanates (ITCs). While it was confirmed that PEITC does induce QR (5 microM required for a two-fold induction in QR), 7-methylsulfinyheptyl and 8-methylsulfinyloctyl ITCs were more potent inducers (0.2 microM and 0.5 microM, respectively, required for a two-fold induction in QR). Thus, while watercress contains three times more phenylethyl glucosinolate than methylsulfinylalkyl glucosinolates, ITCs derived from methylsulfinylalkyl glucosinolates may be more important phase II enzyme inducers than PEITC, having 10 - to 25-fold greater potency. Analysis of urine by liquid chromatography-mass spectroscopy (LC-MS) following consumption of watercress demonstrated the presence of N:-acetylcysteine conjugates of 7-methylsulfinylheptyl, 8-methylsulfinyloctyl ITCs and PEITC, indicating that these ITCs are taken up by the gut and metabolized in the body. Watercress may have exceptionally good anticarcinogenic potential, as it combines a potent inhibitor of phase I enzymes (PEITC) with at least three inducers of phase II enzymes (PEITC, 7-methylsulfinylheptyl ITC and 8-methylsulfinyloctyl ITC). The study also demonstrates the application of LC-MS for the detection of complex glucosinolate-derived metabolites in plant extracts and urine.
Carcinogenesis 2000 Nov
PMID:7-Methylsulfinylheptyl and 8-methylsulfinyloctyl isothiocyanates from watercress are potent inducers of phase II enzymes. 1106 58

Obacunone and limonin are bitter limonoids in citrus. Their modifying effects on the development of aberrant crypt foci (ACF), the activity of detoxification enzymes, glutathione S-transferase (GST) and quinone reductase (QR), and cell proliferation activity were investigated in male F344 rats treated with azoxymethane (AOM). Obacunone and limonin were administered in the diet, during the initiation (for 4 weeks) or postinitiation phase (for 4 weeks) of AOM-induced tumorigenesis. Feeding of obacunone and limonin (0.02% or 0.05%) caused significant reduction (55-65% by "initiation" feeding and 28-42% by "postinitiation" feeding) in the yield of ACF. The ability to reduce the proliferating cell nuclear antigen-labeling index in crypts and correlated well with the prevention of ACF. In a subsequent long-term experiment (38 weeks), in which rats were initiated with AOM and fed 0.05% obacunone or 0.05% limonin during the initiation or post-initiation phase, both compounds in diet caused significant reduction (65%-92% inhibition) in the incidence of colonic adenocarcinoma. Thus, citrus bitter limonoids obacunone and limonin possess chemopreventive effects on chemically induced rat colon carcinogenesis.
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PMID:Citrus limonoids obacunone and limonin inhibit azoxymethane-induced colon carcinogenesis in rats. 1123 84

In an earlier communication, we have shown that Tephrosia purpurea ameliorates benzoyl peroxide-induced oxidative stress in murine skin (Saleem et al. 1999). The present study was designed to investigate a chemopreventive efficacy of T purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N-diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine-initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate-induced lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.01). The depleted levels of glutathione, the inhibited activities of antioxidant enzymes, phase II metabolizing enzymes and the enhanced levels of serum creatinine and blood urea nitrogen were recovered to a significant level (P<0.01). All the antioxidant enzymes were recovered dose-dependently. Our data indicate that T purpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine and KBrO3.
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PMID:Tephrosia purpurea ameliorates N-diethylnitrosamine and potassium bromate-mediated renal oxidative stress and toxicity in Wistar rats. 1145 68

The ability of rosemary to modulate cytochrome P450 (CYP) and detoxication enzymes in rat liver was evaluated by comparing the effects of dried leaves and leaf extracts with different chemical compositions: essential oil (EO) containing monoterpenes, a dichloromethane extract (DCME) containing phenolic diterpenes and a water-soluble extract (WSE) containing phenolic compounds such as rosmarinic acid and flavonoids. Chemical analyses were done in order to characterize the composition of extracts. Male Wistar rats received the leaves or extracts of rosemary in their diet at 0.5% (w/w) for 2 weeks. The effects of such treatments were evaluated for CYP (1A, 2B, 2E1), glutathione S-transferase (GST), NAD(P)H: quinone reductase (QR) and UDP-glucuronosyltransferase (UGT) activities and on protein levels (immunoblot analyses). Expression of specific UGT isoforms (mRNA semi-quantification by RT-PCR) was measured. Our study reports that EO selectively induced CYP, particularly CYP2B. WSE enhanced both CYP and detoxication enzymes. DCME acted as a monofunctional inducer, inducing GST, QR and UGT, in particular UGT1A6. Considering the specific pattern of induction obtained with DCME and WSE treatment, it should be relevant to evaluate the chemopreventive potency of these extracts on carcinogenesis in animal models.
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PMID:Induction of cytochrome P450 and/or detoxication enzymes by various extracts of rosemary: description of specific patterns. 1149 67

We examined the modifying effect of whole-leaf Aloe arborescens Miller var. natalensis Berger (designated as 'ALOE') on azoxymethane (AOM)-induced aberrant crypt foci (ACF), putative preneoplastic lesions, in the rat colorectum. Male F344 rats (4 weeks old) were fed the basal diet, or experimental diets containing 1% or 5% ALOE for 5 weeks. One week later, all rats except those in the vehicle-treated groups were injected s.c. with AOM (15 mg/kg, once weekly for 3 weeks). At 9 weeks of age, all the rats were killed, and the colorectum and liver were evaluated for ACF and cytosolic quinone reductase (QR; a phase 2 enzyme), respectively. In rats given AOM and ALOE (1% or 5% in diet) the numbers of ACF/colorectum, aberrant crypts/colorectum, aberrant crypts/focus and large ACF/colorectum were significantly decreased compared with those of rats given AOM alone (all p < 0.01). No ACF were found in rats treated without AOM. In addition, ALOE significantly increased cytosolic QR activity in the liver (p < 0.01). These results indicated that ALOE inhibited the development of AOM-induced ACF in the rat colorectum, with increased QR activity in the liver, and therefore suggested that ALOE might have a chemopreventive effect against colon carcinogenesis at least in the initiation stage.
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PMID:Inhibition of azoxymethane-induced aberrant crypt foci formation in rat colorectum by whole leaf Aloe arborescens Miller var. natalensis Berger. 1174 64


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