Propylene oxide mutagenesis at template cytosine residues
✍ Scribed by Elizabeth T. Snow; Jatinder Singh; Karen L. Koenig; Jerome J. Solomon
- Book ID
- 102833582
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 689 KB
- Volume
- 23
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
Propylene oxide (PO) is a widely used industrial reagent which is mutagenic and carcinogenic.
We have recently shown that a variety of aliphatic epoxides, including propylene oxide, can reoct with DNA to form hydroxyalkyl adducts at N-3 of cytosine which rapidly undergo hydrolytic deamination to produce uracil adducts. These 3-hydroxyalkyl uracil adducts are stable in DNA and are postulated to be an important class of potentially mutagenic lesions. Mutagenesis at cytosine residues due to PO modification of single-stranded M13mp2K141 DNA was studied by transfection of modified DNA into SOS and non-SOS induced E. coli host cells. Mutations of the proline (CCC) codon at C141 which result in reversion of the IacZ phenotype (blue plaques) were scored. It was found that PO treatment of single-stranded DNA results in dose-dependent mutagenesis that is highly SOS dependent. The spectrum of base-substitution mutations found at this site differed when POmodified DNA was transfected into E. coli with different DNA repair backgrounds. These results indicate that propylene oxide induced DNA adducts at template cytosine residues are mutagenic in E. coli and that this mutagenesis is greatly increased by SOS processing. They also show that these lesions may be repaired by one or more mechanisms.