Environmental chemicals can exert their effects on humans via their mutagenic, cytotoxic and/or epigenetic consequences on cells. Since many volatile organic chemicals (VOC's have been suspected as carcinogens and since they are widespread pollutants in ground water, the potential risk they might pose to human health, alone or in combination, depends on our understanding of their mechanisms of action. Many of these chemicals have not been shown to be genotoxic; therefore, this proposal aims to examine the potential consequences these chemicals might have in altering membrane-dependent endpoints at the molecular, biochemical and cellular levels, in vitro and in vivo, using rat liver cells. Specifically, molecular probes will be used to detect the expression of various oncogenes in rat liver cells exposed to various VOC's, alone and in mixtures, in vivo and in vitro. On the cellular level, these same chemicals will be used to study if and how they might modulate gap junctional intercellular communication in rat liver cells. On the whole animal level, the chemicals will then be tested as potential tumor promoters in the rat liver initiation/promotion system. The objective will be to determine if either altered oncogene expression and modulated intercellular communication might be either altered oncogene expression and modulated intercellular communication might be used as predictive and convenient """"""""biomarkers"""""""" of any tumor promoting potential of these VOC's and to provide basic information regarding the molecular and cellular mechanisms by which these chemicals might exert their toxic effects by """"""""epigenetic"""""""" mechanisms.
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