Carcinogenic compounds under experimental conditions

Many questions in the investigation of a possible mechanism for antioxidant inhibition of mammary carcinogenesis have led us to the need to be able to measure actual tissue concentrations of these compounds. Since BHT was found to be a very effective mammary tumor inhibitor in this model, and BHA to have no measurable effect under the same experimental conditions, one has to ask the question as to whether or not both are absorbed and taken up by the tissues, specifically mammary tissue, since this is the target tissue. BHT was not effective as an inhibitor when fed for three weeks from weaning, then stopped one week prior to carcinogen treatment (35). 

Induction of hepatic enzyme-altered foci (ATPase, GGTase) was investigated after administration of vinyl acetate (200 and 400 mg/kg/day, orally) to newborn rats for 3 weeks, with or without subsequent promotion by phenobarbital (57). No foci were observed in vinyl acetate-treated animals at the age of 14 weeks, whereas the structurally related compounds vinyl carbamate and vinyl chloride induced enzyme-altered foci under comparable experimental conditions. The negative result was not surprising considering the short exposure period and relatively low doses compared to the carcinogenicity studies discussed above. 

There is no evidence to support a causal association between selenium compounds and cancer in humans. In fact, some epidemiological and experimental evidence suggests that selenium exposure under certain conditions may contribute to a reduction in cancer risk. Currently, the chemopreventive potential of selenium is under research. Selenium sulfide and ethyl selenac are the only selenium compounds that have been shown to be carcinogenic upon oral administration in rodents however, significant exposure to these forms of selenium is extremely unlikely. 

Two chapters in this volume describe the generation of carbocations and the characterization of their structure and reactivity in strikingly different milieu. The study of the reactions in water of persistent carbocations generated from aromatic and heteroaromatic compounds has long provided useful models for the reactions of DNA with reactive electrophiles. The chapter by Laali and Borosky on the formation of stable carbocations and onium ions in water describes correlations between structure-reactivity relationships, obtained from wholly chemical studies on these carbocations, and the carcinogenic potency of these carbocations. The landmark studies to characterize reactive carbocations under stable superacidic conditions led to the award of the 1994 Nobel Prize in Chemistry to George Olah. The chapter by Reddy and Prakash describes the creative extension of this earlier work to the study of extremely unstable carbodications under conditions where they show long lifetimes. The chapter provides a lucid description of modern experimental methods to characterize these unusual reactive intermediates and of ab initio calculations to model the results of experimental work. 

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