Ide_2004_Cancer.Lett_214_35

7,12-Dimethylbenz[a]anthracene (DMBA) is a well-known polycyclic aromatic hydrocarbon (PAH) that causes a variety of tumors in exposed animals. Although PAH carcinogenicity is primarily mediated by the aryl hydrocarbon receptor (AhR) through induction of P450, it is not precisely determined whether AhR regulates the DMBA carcinogenesis in vivo. In this context, we examined the frequency of DMBA-induced tumors and the expressions of mRNAs of P450-CYP1 subfamily and microsomal epoxide hydrolase (mEH) in the skin and submandibular gland using AhR-deficient mice. After DMBA exposure, AhR-/- and AhR+/+ mice showed the same tumor incidences and latency. CYP1A1 was absent in these tissues but was slightly induced in DMBA-treated AhR+/+ mice. In AhR-/- and AhR+/+ mice, constitutive expression of CYP1B1 was evident at equivalent levels, whereas CYP1A2 was not detectable, irrespective of DMBA treatment. mEH was expressed in both tissues of all animals. Collectively, the constitutive levels of CYP1B1 and mEH in the skin and submandibular gland maintain DMBA response in these tissues of AhR-/- mice.