Coexpression of human CYP1A2 and N-acetyltransferase 2 in Chinese hamster ovary cells results in high cytotoxicity for carcinogenic heterocyclic amines

Abstract

Chinese hamster ovary (CHO) cell line stably expressing human CYP450 1A2 (CYP1A2), NADPH-CYP450 reductase (CYPR) and N-acetyltransferase 2 (NAT2) was established. The expression of three proteins was determined by Western blot analyses. The introduction of NAT2 cDNA to CHO.1A2BC-RSV which had been transfected with CYP1A2 and CYPR that previously established. The cytotoxicity assay and micronucleus test of 2-aminoanthracene (2-AA), 2-amono-3,4-dimethylimidazo[4,5-f]quinoxaline (MeIQx) were approximately 1,000- and 100-fold more sensitive than CHO.1A2BC-RSV cells. There were no clear differences in sensitivity treated with 2-aminofluorene (2-AF) and 2-amino-1-metyl-6-phenylimidazo[4,5-b]pyridine (PhIP). On the basis of results obtained in this study, it is suggested that the simultaneous expression of CYP1A2, CYPR and NAT2 can be used as a good research model for in vitro metabolic activation.