Morphological transformation of BALB/3T3 cells by various procarcinogens in the presence of a rat liver S-9 activation system.
An Aroclor-induced rat hepatic S-9 metabolic activation system was incorporated into the BALB/3T3 cell transformation assay to increase its sensitivity to a wide range of procarcinogens. S-9 was prepared from Aroclor 1254-induced (500 mg/kg) Fischer 344 rats. Cyclophosphamide, dimethylnitrosamine, 2-aminofluorene, and 2-naphthylamine were metabolized to reactive forms capable of inducing both dose-dependent toxicity and morphological transformation of BALB/3T3 cells. Treatments without an exogenous metabolic activation system were nontoxic and nontransforming. Adaptation of this commonly used exogenous metabolic activation system to BALB/3T3 cells will allow detection of the transforming potential of procarcinogens which test negative in a standard assay.
McCarvill
J T
JT
Division of Genetic and Cellular Toxicology, Microbiological Associates Inc., Rockville, Maryland.
Lubet
R A
RA
Schechtman
L M
LM
Kouri
R E
RE
Putman
D L
DL
D015081:2-Naphthylamine / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003520:Cyclophosphamide / Q000493:pharmacokinetics / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D005449:Fluorenes; C012177:2-aminofluorene; D003520:Cyclophosphamide; D015081:2-Naphthylamine; D004128:Dimethylnitrosamine