Identification of novel 7,12-dimethylbenz[a]anthracene adducts in cellular RNA

Abstract

The interaction of guanosine with 7,12-dimethylbenz[a]anthracene (DMBA) 5,6-oxide under alkaline conditions resulted in the formation of 6 derivatives. These 6 compounds were cochromatographed with nucleosides obtained by hydrolysis of RNA isolated from rat liver cells treated with [3H]DMBA. The cochromatography showed that 3 of these adducts were formed in cellular RNA. The 3 products constituted < 5% of the total nucleoside-DMBA adducts as shown by chromatography on Sephadex LH-20 and high-pressure liquid chromatography. In 1 derivative the 2''-hydroxy group of the ribose moiety of guanosine was linked to the C-5, and in the 2nd it was limited to the C-6 position of the DMBA 5,6-oxide residue. In the 3rd derivative the C-8 position of guanosine was linked to the C-5 of the DMBA 5,6-oxide moiety. These results show for the 1st time modifications of the ribose moiety and of the guanine residue at the C-8 position in the cellular RNA by a metabolite of a polycyclic hydrocarbon.