Cytogenetic effects of promutagens in genetically engineered V79 Chinese hamster cells expressing cytochromes P450.
V79 Chinese hamster cell lines genetically engineered to express rat CYP2B1, CYP1A1, CYP1A2, and their parental cell lines V79-MZ, without acetyltransferase, and V79-NH, with acetyltransferase, were studied for chromosome aberrations and sister chromatid exchange induced by aflatoxin B1, cyclophosphamide, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene and dimethylnitrosamine. The parental V79 cell lines did not show clastogenic effects. Significant clastogenic effects were observed after an 18 h exposure to aflatoxin B1 and cyclophosphamide in CYP2B1 expressing cells, to benzo[a]pyrene in CYP1A1 and CYP1A2 expressing cells, to 7,12-dimethylbenz[a]anthracene and dimethylnitrosamine in cells, expressing CYP1A2 with or without acetyltransferase, and to cyclophosphamide in cells expressing both CYP1A2 and acetyltransferase. A significant sister chromatid exchange inducing effect was found after a 24 h exposure in each of the genetically engineered cell lines, except for benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in CYP2B1 expressing cells, and for benzo[a]pyrene in cells expressing both CYP1A2 and acetyltransferase. Thus, a battery of cell lines genetically engineered for metabolic competence may serve as a tool for investigating chromosomal changes induced by activated xenobiotics.
Kulka
U
U
GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Institut für Strahlenbiologie, Neuherberg, Germany.
Doehmer
J
J
Glatt
H R
HR
Bauchinger
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D016604:Aflatoxin B1 / Q000633:toxicity; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D001711:Biotransformation; D002460:Cell Line; D002869:Chromosome Aberrations / Q000235:genetics*; D006224:Cricetinae; D003412:Cricetulus; D003520:Cyclophosphamide / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004128:Dimethylnitrosamine / Q000633:toxicity; D005818:Genetic Engineering; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity*; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D009153:Mutagens; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D004128:Dimethylnitrosamine