Comparative studies of MCL-5 cells and human lymphocytes for detecting indirect-acting clastogens.
The MCL-5 cell line was established from human lymphoblastoid TK+/- cells transfected with cDNAs of human cytochrome P450s (CYP1A2, CYP2A6, CYP2E1, and CYP3A4) and microsomal epoxide hydrolase. The TK+/- cells constitutively express a relatively high level of endogenous CYP1A1. To study metabolic activities to indirect-acting clastogens, MCL-5 cells were treated with four clastogens, i.e. aflatoxin B1 (AFB1), diethylnitrosamine (DEN), cyclophosphamide (CPA), and 7,12-dimethylbenz[a]anthracene (DMBA). Human lymphocytes from peripheral blood were used as control cells under the assay conditions with or without induced rat liver metabolic activation (S9). All chemicals tested without S9 induced chromosomal aberrations (CA) in MCL-5 cells but not in human lymphocytes. All chemicals induced CA in both cell types in the presence of S9.
Yamakage
K
K
Department of Cellular and Genetic Toxicology, Hatano Research Institute, Food and Drug Safety Center, Hadano, Kanagawa, Japan.
Kusakabe
H
H
Tanaka
N
N
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000493:pharmacokinetics / Q000633:toxicity; D016604:Aflatoxin B1 / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000493:pharmacokinetics / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004052:Diethylnitrosamine / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013937:Thymidine Kinase / Q000172:deficiency / Q000378:metabolism; D014162:Transfection
D007527:Isoenzymes; D009153:Mutagens; D011994:Recombinant Proteins; D004052:Diethylnitrosamine; D015127:9,10-Dimethyl-1,2-benzanthracene; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D013937:Thymidine Kinase; D004851:Epoxide Hydrolases