Skin and salivary gland carcinogenicity of 7,12-dimethylbenz[a]anthracene is equivalent in the presence or absence of aryl hydrocarbon receptor.
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.
Ide
Fumio
F
Department of Oral Pathology, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan. idef@dent.meikai.ac.jp
Suka
Noriyuki
N
Kitada
Munenori
M
Sakashita
Hideaki
H
Kusama
Kaoru
K
Ishikawa
Takatoshi
T
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001551:Benz(a)Anthracenes / Q000494:pharmacology* / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D012333:RNA, Messenger / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000502:physiology*; D012468:Salivary Gland Neoplasms / Q000139:chemically induced* / Q000503:physiopathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000503:physiopathology
D001551:Benz(a)Anthracenes; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C046810:7,12-dihydroxymethylbenz(a)anthracene; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1