Format

Send to

Choose Destination
See comment in PubMed Commons below
Biochemistry. 1996 Sep 3;35(35):11487-92.

1,N6-ethenodeoxyadenosine, a DNA adduct highly mutagenic in mammalian cells.

Author information

  • 1Division of Chemical Carcinogenesis, American Health Foundation, Valhalla, New York 10595, USA.

Abstract

1,N6-Ethenodeoxyadenosine (epsilon dA) is one of four exocyclic DNA adducts produced by chloroethylene oxide and chloroacetaldehyde, reactive metabolites of vinyl chloride, a human carcinogen. epsilon dA has also been detected in DNA of the liver of humans and untreated animals, suggesting its formation from endogenous sources. The mutagenic potential of epsilon dA was studied using a single-stranded shuttle vector system in several E. coli strains and in simian kidney cells (COS7). This vector system enables quantitative analysis of translesional synthesis past a site-specifically placed DNA adduct in both hosts owing to the lack of the complementary strand. In experiments with five strains of E. coli, a very limited number of targeted mutations (one epsilon dA-->T, one epsilon dA-->dC, and two epsilon dA-->single base deletion) were observed among 756 transformants in hosts preirradiated with UV; no targeted mutations were observed among 563 transformants in nonirradiated hosts. These results indicate that nonmutagenic base pairings of epsilon dA:T are the almost exclusive events in E. coli. In COS7 cells, the frequency of targeted mutations was 70%, consisting of epsilon dA-->dG (63%), epsilon dA-->T (6%), and epsilon dA-->dC (1%), indicating that the insertion of dCMP opposite the adduct is predominant. When compared with the results for 3,N4-ethenodeoxycytidine (epsilon dC), which was studied previously in the same system [Moriya et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 11899-11903], the results of this study indicate that the intrinsic mutagenic potency of epsilon dA is comparable to that of epsilon dC in mammalian cells.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Write to the Help Desk