Mutational specificity of alkylating agents and the influence of DNA repair

Journal Article · Mon Jan 01 04:00:00 EST 1990 · Environmental and Molecular Mutagenesis; (USA)

DOI:https://doi.org/10.1002/em.2850150208· OSTI ID:7136197

Horsfall, M J; Gordon, A J; Burns, P A; Zielenska, M; van der Vliet, G M; Glickman, B W ^[1]

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1. York Univ., Toronto, Ontario (Canada)

Alkylating treatments predominantly induce G:C = greater than A:T transitions, consistent with the predicted significance of the miscoding potential of the O6-alG lesion. However, the frequency and distribution of these events induced by any one compound may be diagnostic. SN1 agents that act via an alkyldiazonium cation, such as the N-nitroso compounds, preferentially generate G:C = greater than A:T transitions at 5'-RG-3' sites, while the more SN2 alkylsulfates and alkylalkane-sulfonates do not. The precise nature of this site bias and the possibility of strand bias are target dependent. The extent of this site bias and the contribution of other base substitutions are substituent size dependent. A similar 5'-RT-3' effect is seen for A:T = greater than G:C transitions, presumably directed by O4-alT lesions. The 5'-RG-3' effect, at least, likely reflects a deposition specificity arising from some aspect of helix geometry, although it may be further exaggerated by alkylation-specific repair. Excision repair appears to preferentially reduce the occurrence of ethylation-induced G:C = greater than A:T and A:T = greater than G:C transitions at sites flanked by A:T base pairs. This may be due to an enhancement of the helical distortion imposed by damage at such positions. A similar effect is not seen for methylation-induced mutations and in the case of propyl adducts, the influence of excision repair on the ultimate distribution of mutation cannot be as easily defined with respect to neighbouring sequence. 199 references.

• OSTI ID: 7136197
• Journal Information: Environmental and Molecular Mutagenesis; (USA), Journal Name: Environmental and Molecular Mutagenesis; (USA) Vol. 15:2; ISSN 0893-6692; ISSN EMMUE
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ALKYLATING AGENTS
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
DNA
DNA ADDUCTS
DNA REPAIR
DOCUMENT TYPES
ESCHERICHIA COLI
EXCISION REPAIR
GENETIC EFFECTS
MICROORGANISMS
MUTATIONS
NITROSO COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RECOVERY
REPAIR
REVIEWS
STRUCTURE-ACTIVITY RELATIONSHIPS