Direct acting mutagens

These nltrosated amides, In contrast to the nltrosamlnes, do not require metabolic activation in order to alkylate cellular nucleophilic targets. Thus, many of these substances are directly acting mutagens and also carcinogens (38. ... 

Reaction of benzanthrone with nitrogen dioxide alone or in admixture with ozone gives a mixture of nitrated products including 3-nitrobenzanthrone, which is a new class of powerful direct-acting mutagens of atmospheric origin (Eq. 2.12).26... 

Salmonella typhimurium. Although most nitro PAHs are direct-acting mutagens in Salmonella typhimurium, these compounds must be metabolized to bind covalently to DNA (71,92,112). S. typhimurium contains a family of nitroreductases which are capable of reducing nitro PAHs, and strains which are deficient in these enzymes generally show decreased sensitivity toward nitro PAH-induced mutations (27,92,113-114). These observations suggest that reduced metabolic intermediates may be the critical reactive electrophiles. 

They are direct-acting mutagens towards S. typhimurium TA100 with demonstrable ability to react with plasmid DNA at G-N7 or A-N3. The versatile synthetic protocol has enabled us to synthesise and test, reliably, many representatives and establish a working QSAR that has enabled us to understand intimate details of their interaction with bacterial DNA. Their biological activity can be sheeted home to binding to DNA followed, most likely, by an SN2 reaction with G-N7. Electronic and steric effects of substituents are in accord with this mechanism. 

In bacterial systems, 1,2-dibromoethane is a direct-acting mutagen and primarily causes mutations of the base-pair substitution type (Barber et al. 1981 McCann et al. 1975 Moriya et al. 1983 ... 

Toxicology. Epichlorohydrin is a severe irritant of skin, eye, and respiratory tract. Repeated or prolonged exposure can cause lung liver and kidney damage. It is a direct-acting mutagen and is carcinogenic in experimental animals. 

Epichlorohydrin is a direct-acting mutagen by virtue of its activity as an alkylating agent. ° It causes genetic damage in most bacterial and mammalian test systems in vivo and in vitro. 

In Salmonella typhimurium glycidol is a potent direct-acting mutagen. In vitro it caused an increased number of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells and human lymphocytes. 

In bacterial and mammalian in vitro cell systems TNT is a direct-acting mutagen. However, inclusion of exogenous metabolic activation appears to abolish the genotoxicity. In vivo assays of TNT have not shown it to be genotoxic, suggesting that TNT may be reduced to nonmutagenic metabolic products in the whole animal. 

Tokiwa et al. (1981) reported that direct-acting mutagenic derivatives were formed when pyrene, phenan-threne, fluorene, fluoranthene, and chrysene (and car-bazole) were deposited on filter paper and exposed to... 

Jung, H., A. U. Shaikh, R. H. Heflich, and P. P. Fu, Nitro Group Orientation, Reduction Potential, and Direct-Acting Mutagenicity of Nitro-Polycyclic Aromatic Hydrocarbons, Environ. Mol. Mutagen., 17, 169-180 (1991). 

Stark, G., J. Stauff, H. G. Miltenburger, and I. Stumm-Fischer, Photodecomposition of 1-Nitropyrene and Other Direct-Acting Mutagens Extracted from Diesel-Exhaust Particulates, Mutat. Res., 155, 27-33 (1985). 

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