Toxicity Mutagenesis studies

The importance of active site volume is also evident in the decreasing stere-ospecificity of esterases as the volumes of their active sites increase. In site-specific mutagenesis studies of mammalian AChE, Taylor et al. observed that the stereoselectivity of AChE was reduced 3-fold and 230-fold by substitution of small aliphatic groups for phenylalanine at positions 295 and 297, respectively. Eurthermore, in a comparison of the stereoselectivity of AChE, BChE, and CaE, whose relative active site volumes are 3 5 30, the reported ratio of reaction rates of C(+)P(-) and C(+)P(+) stereoisomers of soman for AChE, BChE, and CaE are 17500, 290, and 135, respectively. " Even though the stereospecificity of CaE is reduced by its larger active site volume in comparison to ChE, it still maintains a 135-fold greater reactivity with the most toxic stereoisomers [i.e., C(+)P(-) soman]. 

Mutagenesis/genetic toxicity studies of AN were scheduled to be initiated in FY 85 (NIEHS, ref. 70, p. 40). 

Epidemiological studies show that dietary fat and protein are most frequently correlated with colon cancer incidence in man (10-14). A number of studies in laboratory animals suggest that dietary fat enhances colon tumor incidence (15) although others have failed to show such enhancement (16). Summarized in this communication are animal experiments conducted by our laboratory to examine the effects of dietary protein on DMH induced carcinogenesis, mutagenesis, and toxicity. 

The NIEHS has sponsored a carcinogenicity study with 4-nitrophenol to be conducted FY 1990 by Litton Bionetics, Inc. (NTP 1990). In addition, NIEHS sponsored a mutagenesis/genetic toxicity study with 4-nitrophenol to be completed FY 1990 the performing organization was not specified (NTP 1990). An acute/chronic toxicity study on 4-nitrophenol sponsored by the FDA was to be completed FY 1990 (NTP 1990). 4-Nitrophenol has been selected for a... 

Most functional proteomic studies have been performed in cancer cell lines, that is, after exposition to toxicants, RNA inhibition, differentiation agents, viral transfection, and so on. These studies covered several aspects of mutagenesis, tumor promotion, and progression. In the recent years, it has been shown that repeated analysis of the proteome at different tumor stages also deliver distinct patterns and thus a functional picture of disease progression at the molecular level. 

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