Mutation spectra of the two guanine adducts of the carcinogen 4-nitroquinoline 1-oxide in Escherichia coil. Influence of neighbouring base sequence on mutagenesis.

Autor: Daubersies, Pierre, Galiégue-Zouitina, Sylvie, Koffel-Schwartz, Nicole, Fuchs, Robert P.P., Loucheux-Lefebvre, Marie-Henriette, Bailleul, Bernard
Zdroj: Carcinogenesis; 1992, Vol. 13 Issue 3, p349-354, 6p
Abstrakt: When the chemical carcinogen 4-nitroquinoline 1-oxide binds to DNA , two major adducts are formed, both at guanine residues, but at different positions, i.e. the C8 or the N2 position. Well-defined adducts (either C8 or N2 guanine adducts) can be formed by reacting DNA with 4-actoxyaminoquinoline 1-oxide (Ac-4HAQO) under different reaction conditions. Forward mutations induced by each of both main 4NQO adducts in the tetracycline resistance gene of pBR322 were determined. In total, 30 independent 4NQO-induced mutations were characterized, showing mainly basepair substitution mutations and some frameshift mutations. We have observed that the 5′ neighbouring base influences the specificity of dGuo-N2-AQO induced base-pair sub-stitutions mutagenesis; a similar effect does not occur with dGuo-C8-AQO. This study reveals the importance of the N2 guanine adduct in the mutagenesis induced by 4NQO . [ABSTRACT FROM PUBLISHER]
Databáze: Complementary Index