Expression of CYP1A in Liver of A/Sn and CC57BR Mice Differing in Sensitivity to Hepatocarcinogenesis Induced by o-Aminoazotoluene

O. A. Timofeeva^1*, M. L. Filipenko¹, N. A. Rychkova¹, L. F. Gulyaeva², and V. V. Lyakhovich²

¹Novosibirsk Institute of Bioorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, pr. Lavrent'eva 8, Novosibirsk, 630090 Russia; fax: (3832) 333-677; E-mail: oa.tim@niboch.nsc.ru

²Novosibirsk Institute of Molecular Biology and Biophysics, Siberian Branch of the Russian Academy of Medical Sciences, ul. Timakova 2, Novosibirsk, 630117 Russia; fax: (3832) 323-147; E-mail: Gulyaeva@cyber.ma.nsc.ru

^* To whom correspondence should be addressed.

Received September 20, 1999; Revision received February 10, 2000

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The induction of P450 cytochromes Cyp1a1 and Cyp1a2 in the liver of male mice differing in sensitivity to the carcinogenic effect of o-aminoazotoluene (OAT) has been studied. The level of Cyp1a1 and Cyp1a2 mRNA was assayed by quantitative competitive polymerase chain reaction (PCR). In both OAT-treated strains, the level of Cyp1a1 mRNA increased more than 1000-fold, while the amount of Cyp1a2 mRNA increased only two- or threefold. Interstrain differences in the Cyp1a mRNA level were revealed. The level of Cyp1a1 mRNA in liver of OAT-induced A/Sn mice was three times higher than in CC57BR mice. The amount of Cyp1a2 mRNA in control and OAT-treated mice was 7 and 13 times higher, respectively, than in CC57BR mice. The enzyme activities of cytochromes P450 1a were assayed. An increase in Cyp1a1 mRNA level in OAT-treated mice correlated with an enhancement of the benzo[a]pyrene hydrolase and 7-ethoxyresofurin o-deethylase activities; the correlation between the level of Cyp1a2 mRNA and 7-ethoxyresofurin o-demethylase activity was much less pronounced. Interstrain variation in Cyp1a1 and Cyp1a2 activities was also shown at the enzyme activity level. We suppose that quantitative differences in the Cyp1a2 mRNA level play a key role in OAT-induced hepatocarcinogenesis.

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KEY WORDS: cytochromes P450 1a, gene expression, induction, o-aminoazotoluene, RT-competitive PCR

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