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7,12-Dimethybenz[a]anthracene (DMBA) is an indirect carcinogen that enlists the host metabolism to produce its ultimate carcinogenic form, and it is known that this metabolism is conducted by cytochrome P450 1A1 and/ or 1B1(CYP1). However, the time course of expression of rat liver CYP1 following DMBA administration has been unclear. After DMBA administration (100 mg/kg b.w.) to SD rats, expression of liver CYP1mRNA was observed at 6 hr and gradually increased with time to peak on days 12, but then disappeared on day 5. Expression of CYP1A1 protein was first observed at 12 hr, peaked on day 2 and decreased on day 5, while expression of CYP1B1 protein was first observed on day 2 and decreased on day 5. Expression levels of CYP1A1mRNA and protein were higher than those of CYP1B1. The present study suggests that high CYP1 enzyme production and DMBA metabolism might occur in rat liver substantially on day 2 following DMBA administration. (J Toxicol Pathol 2003; 16: 287290)

Time Course of Expression of 7,12-Dimethylbenz[a]anthracene-induced CYP1A1 and CYP1B1 mRNA and Protein in Rat Liver