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Site-specific mutagenesis by bulky exocyclic amino-substituted guanine and adenine derivatives in E coli and human cells

  1. Author:
    Moon, K. Y.
    Pauly, G. T.
    Moschel, R. C.
    1. Year of Conference: 1997
  2. Conference Name: Annual Meeting of the American Association for Cancer Research
    1. 38
    2. Pages: A261
  4. Type of Work: Meeting Abstract
  1. Abstract:

    The mutagenicity of the two major DNA adducts produced by 7-bromomethylbenz[a]-anthracene i.e., N2-(benz[a]anthracen-7-ylmethyl)-2'-deoxyguanosine (b[a]a2G) and N6-(benz[a]anthracen-7-ylmethyl)-2'-deoxyadenosine (b[a]a6A) as well as the simpler benzylated analogs N2-benzyl-2'-deoxyguanosine(bn2G) and N6-benzyl-2'-deoxyadenosine (bn6A) was examined in both E. coli and Ad293 human cells. In our E. coli site-specific mutagenesis system none of these aralkylated adducts exhibited any significant mutagenicity with or without SOS induction. In our human cell site-specific mutagenesis system bn2G and bn6A exhibited weak mutagenicity although b[a]a2G and b[a]a6A were significantly mutagenic. At the site of the adduct b[a]a2G produced G to T transversion mutations while b[a]a6A produced A to G transition mutations. These results indicate that the more bulky b[a]a2G and b[a]a6A exhibit significantly greater mutagenicity in human cells than in E. coli and further emphasize the importance of studying site-specific mutagenesis by carcinogen-modified DNA bases in human cells.

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