Differences in murine procarcinogen activation enzymes are not accompanied by parallel differences in procarcinogen-induced sister-chromatid exchange.
C57Bl/6 and DBA/2 mice, strains in which there is marked induction of hepatic monooxygenase activity by phenobarbital, were tested for in vivo sister-chromatid exchange (SCE) formation in response to cyclophosphamide, an agent metabolized by this inducible enzyme system. Baseline SCE frequencies were between 4 and 6 SCEs/cell in regenerating liver and bone marrow of both strains of mice. Administration of cyclophosphamide (5mg/kg) led to an increase of nearly 8 SCEs/cell in both tissues of C57Bl/6 mice and an increase of more than 10 SCEs/cell in DBA/2 mice. Prior exposure to phenobarbital induced p-chloromethylaniline demethylase activity in regenerating liver of both mouse strains approx. 6-fold, but the changes in measured SCE frequencies were not significantly different from those obtained in the absence of enzyme induction. These results, together with our previous observation that induction by 3-methylcholanthrene of benzo[a]pyrene hydroxylase activity in the same mouse strains was not accompanied by a comparable change in benzo[a]pyrene-induced SCE formation, reinforce the impression that simple assays of differences in mixed function oxidase activities may not necessarily be good predictors of hereditary differences in the response to genetic damage by procarcinogens which are presumed to be metabolized by these enzymes.
D000818:Animals; D001564:Benzo(a)pyrene; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001580:Benzopyrenes / Q000378:metabolism*; D001853:Bone Marrow / Q000201:enzymology; D002273:Carcinogens / Q000378:metabolism*; D003434:Crossing Over, Genetic / Q000187:drug effects*; D003520:Cyclophosphamide / Q000378:metabolism*; D004790:Enzyme Induction; D004851:Epoxide Hydrolases / Q000378:metabolism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000201:enzymology; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D001580:Benzopyrenes; D002273:Carcinogens; D001564:Benzo(a)pyrene; D003520:Cyclophosphamide; D001579:Benzopyrene Hydroxylase; C030154:4-chloro-N-methylaniline demethylase; D010089:Oxidoreductases, N-Demethylating; D004851:Epoxide Hydrolases