Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mutagenicity of N-nitrosobis(2-oxopropyl)amine was measured in the V79 assay using homogenates of acinar cells and duct tissue from the pancreases of Syrian hamsters and MRC-Wistar rats as the activating systems. Mutations at the sodium/potassium ATPase and hypoxanthine:guanine phosphoribosyltransferase loci were measured by resistance to ouabain and 6-thioguanine (TG). The order of effectiveness in generating mutagens from BOP was hamster duct, hamster acinar, rat duct, rat acinar. These data show extensive differences in BOP activation by hamster acinar and duct tissue.
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PMID:The mutation of V79 cells by N-nitrosobis(2-oxopropyl)amine activated by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats. 215 24

The metabolic activation of the carcinogens N-nitrosobis(2-oxopropyl)amine (BOP) and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) by Fischer rat and Syrian hamster hepatocytes was investigated in order to determine the existence of species differences in the induction of cell mutation. The conversion of BOP and HPOP into forms mutagenic to V79 cells was studied by using the hepatocyte-mediated mutagenicity assay. Mutations at the hypoxanthine:guanine phosphoribosyltransferase locus and the Na-K-ATPase locus were scored by the induction of 6-thioguanine resistance (TGr) or ouabain resistance (Ouar), respectively. Hepatocytes of both species were capable of converting BOP and HPOP to mutagens for V79 cells in a dose-dependent manner. Metabolism of BOP by rat hepatocytes resulted in higher mutation frequencies than that by hamster hepatocytes. At a BOP concentration of 240 microM, rat hepatocyte metabolism yielded 90.7 TGr mutants and 19.5 Ouar mutants per 10(5) V79 cells. At the same concentration, hamster hepatocyte metabolism of BOP yielded 54.1 TGr mutants and 13.0 Ouar mutants per 10(5) V79 cells. These results did not correlate with the known carcinogenic potency of BOP in the hamster as compared to the rat. Hamster hepatocytes carried out the catabolism of BOP to CO2 at faster rates than rat hepatocytes; therefore, the species difference in mutagenic activation was not due to a defect in BOP uptake or metabolism by hamster hepatocytes. In contrast, metabolism of HPOP by hamster hepatocytes resulted in significantly higher mutation frequencies than that by rat hepatocytes. At an HPOP concentration of 240 microM, hamster hepatocyte metabolism yielded 83.5 TGr mutants per 10(5) V79 cells; rat hepatocyte metabolism yielded only 19.8 TGr mutants per 10(5) V79 cells. This species difference in mutagenic activation correlated well with the known potency of HPOP as a carcinogen for the hamster as compared to the rat. Since hamster pancreatic cells and subcellular fractions are known to have very limited capacity to perform the metabolic activation of HPOP, the results of this study imply that liver metabolism plays an important role in the conversion of HPOP to an agent(s) which subsequently affects the hamster pancreas. The mutagenic potency of BOP versus HPOP was compared after metabolism by hepatocytes from both species. Following their metabolism by hamster hepatocytes, the two compounds were nearly equivalent in mutagenic potency. After metabolism by rat hepatocytes, BOP was significantly more potent mutagen than HPOP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Species specificity in the metabolism of N-nitrosobis(2-oxopropyl)amine and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine to mutagens by isolated rat and hamster hepatocytes. 311 24

A pancreatic acinar cell-mediated mutagenicity assay was developed as an in vitro model system to study the metabolism of N-nitrosobis(2-oxopropyl)amine (BOP) and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amino (HPOP) into forms mutagenic for Chinese hamster V79 cells. Mutations at the hypoxanthine:guanine phosphoribosyltransferase locus and the Na/K ATPase locus were scored by resistance to 6-thioguanine and ouabain, respectively. The ability of both Syrian golden hamster and Fischer rat pancreatic acinar cells to convert BOP and HPOP to mutagens for V79 cells was investigated in order to examine the basis for species specificity. Acinar cells of both species were capable of activating BOP and HPOP to mutagens for V79 cells in a dose-dependent manner. In the 6-thioguanine resistance assay, rat acinar cells induced higher mutation frequencies than hamster acinar cells with both BOP and HPOP. In the ouabain resistance assay, both cell types induced equivalent levels of mutation with the respective nitrosamines. BOP was a considerably more potent mutagen than HPOP after activation by either cell type. This is consistent with the known in vivo specificity of BOP versus HPOP in the hamster pancreas and suggests that BOP may be activated to mutagenic metabolites by a pathway(s) independent from its enzymatic reduction to HPOP. The comparable abilities of rat and hamster acinar cells to convert BOP or HPOP to mutagenic forms imply that pancreatic metabolic activation alone cannot explain the difference in organotropism of BOP and HPOP in the two species.
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PMID:Activation of N-nitrosobis(2-oxopropyl)amine and N-nitroso(2-hydroxypropyl)-(2-oxopropyl)amine to mutagens for V79 cells by isolated hamster and rat pancreatic acinar cells. 405 2