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

The effect of neurotensin on pancreatic carcinogenesis induced by azaserine was investigated in Wistar rats. Rats were given weekly injections of 10 mg/kg body weight of azaserine for 25 weeks and 200 micrograms/kg body weight of neurotensin in depot form every other day for 62 weeks. Carcinogen-induced pancreatic lesions were examined by histochemical techniques, and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histological analysis showed that prolonged administration of neurotensin significantly reduced the volume (as percent of parenchyma) of ATPase-positive pancreatic lesions, which are closely correlated with the ultimate development of pancreatic cancer. Histologically, pancreatic adenocarcinomas occurred at a significantly lower rate in rats treated with neurotensin than in untreated rats. Administration of neurotensin also significantly decreased the labelling indices of carcinogen-induced pancreatic lesions, but not of the surrounding acinar cells. These findings indicate that neurotensin inhibits pancreatic carcinogenesis, and that this may be related to the reduction of ATPase-positive lesions and to the inhibition of cell proliferation in neoplastic lesions of the pancreas.
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PMID:Inhibition by neurotensin of azaserine-induced carcinogenesis in rat pancreas. 199 48

The effect of changing the format of administration as well as the total dose of the promoting agent phenobarbital (PB) on the development of altered hepatic foci (AHF) was determined in an initiation-promotion protocol with female rats fed the purified AIN-76 diet. Effects on the total number of AHF and the volume percentage of liver occupied by AHF were determined for four histochemical markers, the placental form of glutathione S-transferase, gamma-glutamyl-transpeptidase canalicular ATPase, and glucose-6-phosphatase after 16 and 60 weeks of promotion with varying doses and formats of PB, as well as for a further 16-week period in which no PB was administered. At the 16-week point, animals fed 0.1% PB continuously exhibited the largest number and volume percentage of AHF, whereas rats fed 0.1% PB for 4 days followed by 10 days of no PB with continuous repetition of this pattern during the 16-week treatment period exhibited no increase in the number of AHF over control and only a slight increase in volume percentage. Rats fed a continuous repetition of 0.2% PB for 2 days followed by 12 days of no PB exhibited an intermediate increase in the number of AHF as well as the volume percentage fraction after 16 weeks of this regimen. After 60 weeks of feeding PB by these three different formats, the numbers of AHF observed in these groups were equivalent and had increased above those seen after 16 weeks of feeding. The volume percentage occupied by the AHF in these three groups was also similar, although animals receiving 0.2% PB intermittently showed a significantly lower volume percentage than animals receiving 0.1% PB continuously for 60 weeks. When animals were maintained for an additional 16 weeks without PB feeding, the numbers of AHF decreased dramatically, much more so in animals fed PB intermittently, whereas the volume percentage fraction of AHF in livers of animals receiving 0.1% PB continuously for 60 weeks almost doubled. In contrast, the volume percentage fraction of AHF in livers of animals receiving PB intermittently for 60 weeks followed by 16 weeks of no PB was slightly less. Examination of the individual size classes of AHF showed little change in their distribution at 16 and 60 weeks, but after 16 weeks of PB withdrawal (76 weeks total time), the distribution of AHF in animals that had received 0.1% PB continuously for 60 weeks exhibited a decidedly greater shift to larger AHF than animals receiving PB intermittently for the 60-week period.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1991 Jun
PMID:The effect of the format of administration and the total dose of phenobarbital on altered hepatic foci following initiation in female rats with diethylnitrosamine. 204 80

The purpose of this study was to determine if the dietary antioxidant selenium could inhibit hepatocarcinogenesis induced by peroxisome proliferators, which are hypothesized to induce tumors by increased production of hydrogen peroxide or other reactive oxygen species. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (0.04, 0.2, or 1.0 ppm) of selenium for 6 or 21 months. The incidence of hepatic tumors and the number and volume of gamma-glutamyl transpeptidase-positive, ATPase-negative, glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci at 21 months were lower in rats fed higher levels of selenium (no foci or tumors were seen at 6 mo). Indices of oxidative damage in the liver (thiobarbituric acid reactants, conjugated dienes, and lipid-soluble fluorescence products), however, were not decreased in rats fed the high-selenium diet. Therefore, selenium was protective against ciprofibrate-induced hepatocarcinogenesis, but not by reducing the degree of oxidative damage. The liver selenium and glutathione concentrations, and liver selenium-dependent glutathione peroxidase activity, increased as dietary selenium increased. Therefore, inhibition of carcinogenesis by selenium was correlated with increased levels of glutathione and glutathione peroxidase, but these did not inhibit the indices of oxidative damage. Peroxisomal beta-oxidation also increased with the dietary selenium content; it therefore does not appear to be a factor in the inhibition of hepatocarcinogenesis in rats fed higher levels of selenium.
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PMID:Effect of dietary selenium on the induction of altered hepatic foci and hepatic tumors by the peroxisome proliferator ciprofibrate. 208 22

The kinetics of induction and growth of acinar cell lesions has been investigated in rat pancreas after a single dose of the carcinogen azaserine. The time--response relationship was studied in male Wistar-related rats given a single i.p. injection of 30 mg L-azaserine/kg body weight at 18 days of age. Rats were killed between 4 and 78 weeks after treatment and ATPase-stained pancreas sections were quantitatively evaluated for the number and size of acidophilic, ATPase-positive and basophilic, ATPase-deficient foci. The number of acidophilic foci remained constant from 8 weeks onwards, while the number of basophilic foci slightly increased with time. The size of both acidophilic and basophilic foci increased throughout the experimental period. Due to two times higher number/cm3 and faster growth of the acidophilic foci, four times more acidophilic than basophilic focus tissue was present at the end of the experiment. Progression of acidophilic foci to adenomas and carcinomas was occasionally seen at later time points (greater than 34 weeks) in this rat strain. The dose--response relationship was studied in male and female Sprague--Dawley rats given a single i.p. injection of 0-45 mg azaserine/kg body weight at 19 days of age. Rats were autopsied at 17 weeks after treatment, and pancreas sections were quantitatively evaluated after ATPase histochemistry. The relationship between dose and number of foci was linear up to 30 mg/kg azaserine for both acidophilic and basophilic foci in males and females. For each individual dose, the number of foci induced was the same in males and females, and there were two to three times more acidophilic than basophilic foci. The percentage of pancreatic tissue occupied by focus tissue was 1.75 times higher in males, pointing to a higher growth-potential of acidophilic foci in males than in females. The first-order dose--response kinetics indicate that the conversion of a normal acinar cell into a focus-forming cell occurs by one specific azaserine-mediated rare event, occurring probably at the genetic level of the target cell.
Carcinogenesis 1990 Feb
PMID:Kinetics of induction and growth of putative precancerous acinar cell foci in azaserine-induced rat pancreas carcinogenesis. 213 81

The ability of methyl-deficient, amino-acid-defined diets to produce enzyme-altered foci was quantitatively determined in the livers of rats treated both with and without an initiating dose of diethylnitrosamine (DEN). Male weanling F-344 rats were fed a complete, amino-acid-defined diet for 1 week. They were then injected i.p. with a single dose of DEN (20 mg/kg body weight) and fed the complete diet for an additional week. Forty animals in each dose group were then maintained for 5-38 weeks on the complete diet (diet 1) or one of the three methyl-deficient diets customarily used in this laboratory: diet 2, devoid of methionine and choline; diet 3, devoid of methionine only; and diet 4, devoid of choline only. In diets 2 and 3, methionine was replaced by equimolar amounts of its metabolic precursor, DL-homocystine. Ten animals per group were killed 8, 12, 17, 24 and 41 weeks after DEN initiation. For 2 weeks prior to being killed, each group was maintained on the complete diet to minimize the histological abnormalities due to acute toxicity of the diets. Serial sections of the livers were obtained, stained sequentially for gamma-glutamyltranspeptidase, ATPase and glucose-6-phosphatase, and the quantitation of the focal lesions scored by these markers was carried out by quantitative stereology. The results indicated that, regardless of the enzyme marker(s) examined, there was a general correspondence between the volume and number of altered hepatic foci (AHF) formed and the previously described tumor-promoting activities of each diet. Thus, while all DEN-treated groups contained significant numbers of AHF 24 weeks after initiation, only the diet-2-fed animals displayed such foci at 8 weeks. Similarly, among the uninitiated rats, only those fed diet 2 exhibited the presence of AHF throughout the experimental period. Interestingly, the livers of uninitiated, choline-deficient rats showed a small number of AHF at 24 and 42 weeks; these foci were not observed at all in the corresponding DEN-untreated animals fed diet 3, deficient in methionine only. The results provide evidence that the carcinogenic effects of the methionine- and choline-deficient diet result more from its strongly promoting effect than from any initiating activity by the diet.
Carcinogenesis 1990 Feb
PMID:The effect of choline and methionine deficiencies on the number and volume percentage of altered hepatic foci in the presence or absence of diethylnitrosamine initiation in rat liver. 230 54

Enzyme-histochemical investigation of pancreatic carcinogenesis in male Wistar rats treated at the age of 19 days by a single dose of 30 mg azaserine/kg body wt led to the detection of a new 'marker' for the recognition of foci of atypical acinar cells: the Mg2+-dependent ATPase. The two well-known populations of pancreatic atypical acinar cell foci, classified histologically as basophilic and acidophilic foci, showed a decreased and strongly increased ATPase reaction, respectively. The enhanced enzyme activity of the acidophilic foci has been characterized as unspecific nucleoside polyphosphatase. To validate the new marker, comparative quantitative evaluation was performed on haematoxylin and eosin-stained paraffin sections and ATPase-stained cryostat sections of the same pancreata of 25 azaserine-treated rats. Evaluation of basophilic ATPase-deficient foci of small diameter was more reproducible in haematoxylin and eosin-stained sections, while small acidophilic strongly ATPase-positive foci could be detected more reliably by the ATPase staining technique. The number of foci/cm3 pancreas was similar for both staining techniques above a focus diameter of about 100 microns for basophilic foci and 200 micronfor acidophilic foci. There were more acidophilic than basophilic foci/cm3 pancreas, and the acidophilic foci had significantly larger mean focal diameters than the basophilic foci. Together with the strong acidophilic staining of the latter emerging adenoma, this suggests that the acidophilic foci represent a neoplastic cell population progressing eventually to pancreatic carcinoma. The new 'marker' enzyme ATPase may greatly facilitate further investigations into the role of these putative preneoplastic lesions in pancreatic carcinogenesis.
Carcinogenesis 1986 Mar
PMID:Adenosine triphosphatase, a new marker for the differentiation of putative precancerous foci induced in rat pancreas by azaserine. 241 8

5-Azacytidine (5-aza-CR) and six of its analogs were examined for their ability to induce trifluorothymidine (TFT) and/or 6-thioguanine (6TG) resistance in L5178Y mouse lymphoma cells. These analogs were 5-aza-2'-deoxycytidine (5-aza-CdR), 5-fluoro-2'-deoxycytidine (5-FCdR), 5,6-dihydro-5-azacytidine (dH-aza-CR), 6-azacytidine (6-aza-CR), cytidine (CR) and 1-b-D-arabinofuranosylcytosine (ara-C). 5-Aza-CR and 6-aza-CR were examined for their ability to induce 6TG-resistant colonies and results demonstrated no effect. At least a 5-fold increase in TFT resistance was observed for 5-aza-CR, 5-aza-CdR, 5-FCdR, dH-aza-CR and ara-C. The concentration at which these compounds induced TFT resistance correlated well with the potential of the nucleoside analogs to induce differentiation in C3H10T1/2 cells as determined by Constantinides et al. (Nature, 267, 364-366, 1977). In L5178Y mouse lymphoma (MOLY) cells, 5-aza-CR induced TFT resistance and produced both small and large colonies. Previous studies using mammalian cells showed the absence of mutagenic activity with 5-aza-CR and some of its analogs at the ATPase and hgprt loci. However, the different spectrum of DNA lesions detected at the tk locus may be responsible for the response of MOLY cells to 5-aza-CR.
Carcinogenesis 1989 Nov
PMID:TFT and 6TG resistance of mouse lymphoma cells to analogs of azacytidine. 247 9

The ability of mutagens to transform benign papillomas to malignancy in the mouse skin model of multistage carcinogenesis [Hennings et al. Nature 303, 67-68 (1983)] suggests that multiple events may underlie carcinogenic progression, and that mutagenic exposures separated by time can act synergistically. Such synergism may result from initial mutagenic exposure which induces heritable sensitivity to subsequent mutagenic exposures. For example, progeny of X-irradiated V79 cells are hypersensitive to subsequent mutation induced by psoralen plus long-wave ultraviolet light, PUVA [Frank and Williams, Science 216, 307-308 (1982)]. In the present studies 100 to 200 surviving clones of short-wave ultraviolet light (UVC) irradiated V79 cells were assayed for mutation at two loci. Cultures derived from these cells were found to be hypermutable at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus following exposure to PUVA, but showed mutant frequencies similar to control cells following UVC challenge at the HGPRT and ATPase loci.
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PMID:Heritable hypersensitivity to induced mutagenesis in the progeny of cell populations exposed to UVC (254 nm). 252 33

Thirty-seven adult male and female golden hamsters (Mesocricetus auratus) were divided into four experimental groups. In Group A, the animals served as untreated controls, having the left buccal pouches painted with mineral oil. In Group B, the animals received 10 mg vitamin E (alpha tocopherol) in peanut oil by the oral route, with a fine pipette, twice weekly. In Group C animals, the left buccal pouch was painted three times weekly with DMBA (0.5% solution of 7,12 dimethylbenz(a)anthracene in heavy mineral oil). Group D animals received both vitamin E and DMBA in the amounts indicated for Groups B and C, with the vitamin E being administered on days alternate to the DMBA painting, also in the manner described for the above groups. All animals were killed after eight weeks of treatment. Epithelial whole mounts were prepared from the left buccal pouches. These specimens were then stained for ATPase to demonstrate the presence of Langerhans cells (LCs). A notably decreased density of LCs was observed after treatment with DMBA. Vitamin E administration in addition to DMBA treatment resulted in a less dramatic decrease in LC density. Since vitamin E has been shown to retard experimental oral carcinogenesis, vitamin E may retard carcinogenesis by maintaining the number of Langerhans cells.
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PMID:Alpha tocopherol alters the distribution of Langerhans cells in DMBA-treated hamster cheek pouch epithelium. 257 13

ATPase-deficient foci in rat liver, considered to be clonal in origin and possible precursors of hepatocellular carcinomas, were induced by injecting male Wistar AF/Han (200-220 g) rats with N-methyl-N-nitrosourea (MNU) (25 mg/kg) 16 or 22 h after partial hepatectomy and feeding for 80 days with a diet containing phenobarbital. The animals were killed after 90 days and the intralobular distribution of the preneoplastic foci was analysed quantitatively. The locations of 48 foci in the 16-h group and 22 foci in the 22-h group were determined from serial sections and blocks of liver from five animals. The mean distance of the foci from the portal vein in the 16-h group (385 microns) was 30% less than the distance of randomly selected points (546 microns), while the mean distance of the foci in the 22-h group (450 microns) was 16% less than the random points (535 microns). The mean diameter of the foci (235 microns) was 17% greater in the 22-h group than in the 16-h group (196 microns). We suggest that the cells in early S phase which are periportally situated 16 h after partial hepatectomy and occupy an intermediary position at 22 h represent the sensitive target population for initiation.
Carcinogenesis 1989 May
PMID:Intralobular distribution of preneoplastic foci in rat liver after a single dose of N-methyl-N-nitrosourea (MNU) following partial hepatectomy. 270 42


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