Occupational skin cancer/tumor

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. 

Cancer was first recognized as an occupational hazard in 1775 when the prevalence of scrotal cancer among London chimney sweeps was noticed. The chemical origin of this form of cancer was not universally accepted until 1922 when it was demonstrated that tumors could be induced on mouse skin using an etheral soot extract (60). Skin cancer was also noted to be an occupational hazard of workers exposed to pitch dust in the coal-briquetting industry (61) and to workers exposed to cmde tar (62). In 1915, tumors were produced in rabbits ears by prolonged application of cmde coal tar (63). Some 38 cases per year have been reported of cutaneous epithelioma in the tar distilling industry over a 25-year period up to 1945 (64). 

The discovery that exposure to exogenous chemicals could lead to cancer in humans was first made in the late 18th century, when Percival Pott demonstrated the relationship between cancer of the scrotum and the occupation of chimney sweepers exposed to coal tar/soot. Other examples noted later were scrotal cancers in cotton spinners exposed to unrefined mineral oils, and cancers of the urinary bladder in men who worked in textile dye and rubber industries due to their exposure to certain aromatic amines used as antioxidants. Experimental induction of cancer by chemicals was first reported in detail by Yamagiwa and Ichikawa in 1918, when repeated application of coal tar to the ear of rabbits resulted in skin carcinomas. Over the next few years, Kennaway and Leitch confirmed this finding and demonstrated similar effects in mice and rabbits from the application of soot extracts, other types of tar (e.g., acetylene or isoprene), and some heated mineral oils. These researchers also observed skin irritation sometimes accompanied by ulcers at the site of application of the test material. Irritation was thought to be an important factor in skin tumor development. However, not all irritants (e.g., acridine) induced skin cancer in mice and conversely, some purified chemicals isolated from these crude materials... 

Another study was located that reported that there was no increase in the risk of skin, bladder, or lung cancer in wood treatment plant workers, where coal tar creosote and coal tar pitch were the chemicals used (TOMA 1980). Nevertheless, these findings are of limited value since the study population was limited to those currently working at the plant, was small, and comprised of 46.5% blacks, who experience a very low incidence of skin cancer compared to whites. In addition, the exposure and follow up periods did not allow a long enough latency period for tumor development and there was no verification provided that those studied were actually exposed to coal tar creosote or coal tar. No association was found between bladder cancer and occupational exposures to coal tar and pitch or creosote in a case-control study of 484 persons with confirmed bladder cancer (Siemiatycki et al. 1994). 

Use of lead arsenate as a pesticide was also cancelled on most crops - the basis for the cancellation being two-fold -the irreversibility of neurological damage resulting from lead exposure of children and the potential for lead-induced renal tumors noted at high levels in rodents resulted in a requirement to reduce the total lead exposure from all soxirces, and secondly the occupational exposure data indicates the potential for human skin cancer resulting from arsenic exposure. 

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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