Environmental and Molecular Mutagenesis · 1990 · 10 citations · 24 references
PharmacyPharmacologyToxicologyCarcinogenesisHepatotoxicologyMetabolismCarcinogen MetabolismCarcinogenic MechanismsCarcinogenicity AssessmentHepatic ToxicityHepatotoxicity MechanismsMolecular Mechanisms Of ToxicityAssayCarcinogenic Hepatic EffectsHepatotoxic MechanismsMechanisms Of CarcinogenicityMetabolic Activation Of ProcarcinogensMorphological TransformationToxic MetabolitesToxicology Screening Models
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.
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