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Association between Mutation Spectra and Stable and Unstable DNA Adduct Profiles in Salmonella for Benzo[a]pyrene and Dibenzo[a.l]pyrene
Citation:
DEMARINI, D. M., N. M. HANLEY, S. H. WARREN, L. D. ADAMS, AND L. C. KING. Association between Mutation Spectra and Stable and Unstable DNA Adduct Profiles in Salmonella for Benzo[a]pyrene and Dibenzo[a.l]pyrene. MUTATION RESEARCH. Elsevier Science Ltd, New York, NY, 714(1-2):17-25, (2011).
Impact/Purpose:
This paper shows that the air pollutant dibenzo[a,l)pyrene induces mutations via stable DNA adducts, whereas the much less potent (but more prevalent) benzo[a)pyrene induces mutations via stable DNA adducts and ossibl unstable adducts.
Description:
Benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) are two polycyclic aromatic hydrocarbons (PAHs) that exhibit distinctly different mutagenicity and carcinogenicity profiles. Although some studies show that these PAHs produce unstable DNA adducts, conflicting data and arguments have been presented regarding the relative.roles ofthese unstable adducts versus stable adducts, as well as oxidative damage, in the mutagenesis and tumor-mutation spectra of these PAHs. However, no study has determined the mutation spectra along with the stable and unstable DNA adducts in the same system with both PAHs. Thus, we determined the mutagenic potencies and mutation spectra of BP and DBP in strains TA98, TAlOO and TAI04 of Salmonella, and we also measured the levels of abasic sites (aldehydic-site assay) and characterized the stable DNA adducts e2P-postlabelingIHPLC) induced by these PAHs in TAI04. Our results for the mutation spectra and site specificity of stable adducts were consistent with those from other systems, showing that DBP was more mutagenic than BP in TA98 and TAIOO. The mutation spectra of DBP and BP were significantly different in TA98 and TAl04, with 24% of the mutations induced by BP in TA98 being complex frameshifts, whereas DBP produced hardly any of these mutations. In TAl04, BP produced primarily GC to TA transversions, whereas DBP produced primarily AT to TA transversions. The majority (96%) of stable adducts induced by BP were at guanine, whereas the majority (80%) induced by DBP were at adenine. Although BP induced abasic sites, DBP did not. Most importantly, the proportion of mutations induced by DBP at adenine and guanine paralleled the proportion of stable DNA adducts induced by DBP at adenine and guanine; however, this was not the case for BP. Our results leave open a possible role for unstable DNA adducts in the mutational specificity of BP but not for DBP. Key words: Mutation spectra, PAHs, DNA adducts, Abasic sites
