The metabolism and detoxification of xenobiotics including drugs and environmental toxicants mainly take place in the liver. A variety of enzymes with overlapping substrate specificity are expressed in the liver and are divided into Phase I (oxidizing) and Phase II (conjugating) drug metabolizing enzymes (DMEs). Approximately 90% of Phase I metabolism is carried out by enzymes belonging to the cytochrome P450 (CYP) superfamily. Mouse CYP2A5 and its human ortholog CYP2A6 belong to the CYP450 family. There are increasing evidence that hepatic CYP2A5 expression and activity was enhanced in the liver exposed to various chemical hepatotoxins and pathophysiological conditions [chemicals (Jounaidi et al., 1994), AFB1 (Pelkonen et al., 1997), microorganism (Sipowicz et al., 1997), carcinoma (Raunio et al., 1998), parasite (Montero et al., 1999)], while levels of most CYP enzymes are either unchanged or decreased (Kojo et al., 1998). CYP2A5/2A6 is coumarin-7-hydroxylase and responsible for the metabolism of nicotine, drugs and procarcinogens such as aflatoxin B1 (AFB1) and nitrosamines (Camus-Randon et al., 1993; Kirby et al., 1994a,b; Felicia et al., 2000). The hepatotoxic compounds that up-regulate CYP2A5/2A6 are structurally unrelated and
