A TRANSVERSION MUTATION HYPOTHESIS FOR CHEMICAL CARCINOGENESIS BY N-2-SUBSTITUTION OF GUANINE IN DNA
A TRANSVERSION MUTATION HYPOTHESIS FOR CHEMICAL CARCINOGENESIS BY N-2-SUBSTITUTION OF GUANINE IN DNA
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DOI：
10.1016/0009-2797(80)90014-9
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发表时间：
1980-01-01
影响因子：
5.1
通讯作者：
KADLUBAR, FF
中科院分区：
文献类型：
--
作者：
KADLUBAR, FF
Several carcinogenic aromatic amines and polycyclic hydrocarbons react covalently with the exocyclic amino group (N2) of guanine in DNA. Space-filling molecular models of DNA containing N2-guanyl adducts of 2-acetylaminofluorene (AAF) or benzo[a]pyrene (BP) were constructed. From these models and from available physicochemical data, it is suggested that the N2 adducts may be easily converted from the normal anti to a syn conformation (base/deoxyribose). This configuration causes minimal distortion of the DNA model with only a 2-3 .ANG. shift in the helical axis of symmetry. Such an alteration may account for the persistence of these adducts in DNA and for the frameshift mutations induced by these carcinogens. The syn N2-guanyl configuration places the N-7 and O6 atoms of the modified syn guanine in the base pairing region such that, during replication, mispairing with N-1 and N2 of an opposite guanine may occur. This would then represent a carcinogen-induced transversion mutation and may lead to neoplastic transformation.
