| Summary: | Two human cell lines, the transformed A549 and the excision deficient XP4Ld, were treated with a series of structurally related compounds prior to estimating cytotoxicity or monitoring DNA damage and its excision repair by incubation with or without araC and alkaline sucrose gradient sedimentation. These experiments were undertaken in an effort to clarify whether certain structural alterations which reduce or abolish the cytotoxic, mutagonic/carcinogenic potency of some powerful mutagens/carcinogens do so by either modifying the type and/or amount of DNA damage induced or were a reflection of the cell's ability to deal effectively with such damage. In addition attempts were made to examine the capacity of A549 cells to activate some procarcinogens. Prior to these studies experiments with various ultraviolet light and X-ray doses were conducted in order to determine the repair rates of these well studied DNA lesions in the cell lines used. The data suggest that (i) the reduction in potency of 4-nitroquinoline1-oxide due to methylation at the three position is a reflection of both a change in the number and types of DNA damage induced; (ii) the reduction in potency of 4-chloromethylbiphenyl due to the removal of a benzyl group to leave benzyl chloride is alone due to a reduction in the amount of DNA damage induced; (iii) the abolition of the potencies of 4-chloromethylbiphenyl and benzyl chloride due to substitution of the hydroxymethyl group for chloromethyl to leave 4-hydroxymethylbiphenyl and benzyl alcohol respectively is because the latter chemicals are incapable of producing a detectable level of DNA damage; (iv) in contrast to previous reports, ethyl methanesulphonate and methyl methanesulphonate induced DNA damage undergo repair at a relatively slow rate in human cells; and (v) A549 cells appear to be capable of activating the procarcinogens 1-naphthylamine, benzo(a)pyrene and 4-dimethylaminoazobenzene, but not 2-naphthylamine and 2-acetylaminofluorene.
|
|---|
