Comparison of microsomal inducer pretreatment on the in vitro alpha-hydroxylation and mutagenicity of N-Nitrosopyrrolidine in rat and hamster liver.
The effect of modifiers of liver mixed function oxidase activity on the in vitro alpha-hydroxylation and mutagenicity of N-nitrosopyrrolidine (NPYR) has been examined in rats and hamsters. Hamster post-mitochondrial supernatants were able to convert NPYR to a mutagen more efficiently than rat preparations under all conditions studied. Aroclor 1254 pretreatment caused the greatest increase in mutagenic activity in both species while phenobarbital and 3-methylcholanthrene pretreatment gave intermediate values when compared to uninduced preparations. Microsomal alpha-hydroxylation of NPYR was induced by Aroclor 1254 pretreatment in both species. Pretreatment with 3-methylcholanthrene increased alpha-hydroxylation in hamsters but decreased it in rats. Phenobarbital pretreatment only slightly increased microsomal alpha-hydroxylation in either species. When microsomal alpha-hydroxylation rates were expressed per gram wet weight of liver, better agreement between rates of alpha-hydroxylation and mutagenicity in phenobarbital pretreated animals was obtained since inducer associated changes in total microsomal protein content were taken into account. An example of differential induction of an activation pathway (alpha-hydroxylation) and a degradative pathway (aldehyde dehydrogenase) is presented to illustrate a potential source of error in the interpretation of metabolic data obtained from post-microsomal supernatants and whole animal studies.
D000818:Animals; D006224:Cricetinae; D004790:Enzyme Induction / Q000187:drug effects; D006900:Hydroxylation; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000201:enzymology*; D009153:Mutagens; D009242:N-Nitrosopyrrolidine / Q000378:metabolism / Q000633:toxicity*; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000235:genetics; D013347:Subcellular Fractions / Q000201:enzymology
D009153:Mutagens; D009602:Nitrosamines; D009242:N-Nitrosopyrrolidine