| Our environment contains many chemical and physical agents, only some of which have been isolated, capable or inducing mutagenic and carcinogenic lesions within DNA. Furthermore, the observable effects of DNA lesions are mediated by one or more DNA repair pathways. To simplify the study of environmental mutagens, therefore, it is necessary to identify the mechanisms by which significant DNA lesions are able to induce specific effects if we are to focus on those agents which present the greatest carcinogenic risk.; In the first study the types of chromosomal aberrations induced by interstrand crosslinks was determined. Photoactivation of 8-methoxypsoralen (8-MOP) in a two step irradiation protocol can be used to increase the number of DNA interstrand crosslinks specifically so as to isolate the effects of crosslinks from other DNA lesions. With this protocol the types of chromosomal aberrations induced by interstrand crosslinks were determined.; The other studies involved the use of fibroblast strains which had been shown previously to be mutagen-hypersensitive. The first of these two studies distinguished among several possible explanations for the discrepancies between separate reports on the sensitivity of Bloom syndrome (BS) fibroblasts to mitomycin C (MMC).; In the second study, a cell strain (46BR), unique in the variety of mutagens to which it is hypersensitive, was tested for its DNA repair capabilities. Host cell reactivation (HCR) of N-methyl-N{dollar}prime{dollar}-nitro-nitrosoguanidine (MNNG) treated adenovirus 2 was used as a biological measure of DNA repair potential. (Abstract shortened by UMI.)... |
