Skin cancer, carcinogen risk assessment

This approach is based on the discovery that carcinogens cause specific mutations in tumors. The unique pattern in UV-induced skin cancers has been identified in the p53-tumor-suppressor gene (Brash et al. 1991 Reid et al. 1992 Somers et al. 1992 Moles et al. 1993 Ziegler et al. 1993 Nakazawa et al. 1994), a key gene which is mutated in more than 50% of all tumors (Greenblatt et al. 1994 HoUstein et al. 1991, 1996). The specific mutations can then be used as a molecular marker for UV-induced skin cancer. We hypothesize that such an indicator can also be found for tar-induced (one example of chemically-induced) SCC skin tumors, which can be differentiated from the genetic marker for UV-induced skin tumors. This proposed study will produce a clearer picture as to the exact nature of occupational skin cancer caused by tar. In addition, it will provide further evidence as to the use of molecular epidemiology in cancer risk assessment. 

Studies of occupational exposures to sulfur mustard indicate an elevated risk of respiratory tract and skin tumors following long-term exposure to acutely toxic concentrations. Overall, several factors are important regarding the assessment of the carcinogenicity of sulfur mustard. Increased cancer incidence in humans appears to be associated only with exposures that caused severe acute effects, and occupational exposures tended to involve repeated exposures and repeated injury of the same tissues. Because the therapeutic use of the sulfur mustard analog nitrogen mustard is associated with an increased incidence of CML, the reports of CML in HD-exposed individuals appear to be relevant to the eareinogenicity of sulfur mustard. 

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