Co-carcinogenesis

While the lung is the major organ exposed to airborne dusts, such agents may also be swallowed following mucociliary transport and removal from the lung. Contaminating particles contained in food and drink also gain direct access into the gut. 

Animal experiments into the effect of ingestion of chryso-tile asbestos demonstrated an accumulation of cellular debris within the lumen of the ileum and colon consistent with cytotoxic changes of the mucosal lining cells (Jacobs etal., 1978). The question as to whether asbestos causes tumours in the gastrointestinal tract in humans is a topic of concern, however, the evidence remains equivocal (Levine, 1985). 

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Pi, J. et al., Low level, long-term inorganic arsenite exposure causes generalized resistance to apoptosis in cultured human keratinocytes Potential role in skin co-carcinogenesis, Int. J. Cancer, 116, 20, 2005. 

Listed in Table 27.11 are a number of co-carcinogenesis models that have been used with CTP and in some cases APT. As with the models listed in... 

Taraxasterol Saussurea lappa, Taraxacum Inhibits TPA co-carcinogenesis... 

The problem is also complicated by the fact that several substances frequently interact. Their mutual activity can have procarcinogenic effects. Thus, the field of co-carcinogenesis is entered, which even further complicates the situation. 

Witschi, H. and Lock, S., 1978, Butylated hydroxytoluene A possible promoter of adenoma formation in mouse lung. In "Carcinogenesis, Vol. 2, Mechanisms of Tumor Promotion and Co-carcinogenesis," T.J. Slaga, A. Sivak, and R.K, Boutwell, eds.. Raven Press, New York. 

P. D. Lawley and co-workers, eds., Topics in Chemical Carcinogenesis University of Tokyo Press, Tokyo, Japan, 1972, 272 pp. 

Maltoni C, Lefemine G, Cotti G. 1986. Experimental research on trichloroethylene carcinogenesis. In Maltoni C, Mehlman MA, eds. Archives of research on industrial carcinogenesis series. Vol. V. Princeton, NJ Princeton Scientific Publishing Co., Inc., 393. 

Human exposure to complex mixtures of polycyclic aromatic hydrocarbons (PAH) occurs through inhalation of tobacco smoke and polluted indoor or outdoor air, through ingestion of certain foods and polluted water, and by dermal contact with soots, tars, and oils CO. Methylated PAH are always components of these mixtures and in some cases, as in tobacco smoke and in emissions from certain fuel processes, their concentrations can be in the same range as some unsubstituted PAH. The estimated emission of methylated PAH from mobile sources in the U.S. in 1979 was approximately 1700 metric tons (2). The occurrence of methylated and unsubstituted PAH has been recently reviewed (1, 2). In addition to their environmental occurrence, methylated PAH are among the most important model compounds in experimental carcinogenesis. 7,12-Dimethylbenz[a]anthracene, one of... 

NTl 73 Bock, F. G., and D. F. Clausen. Further fractionation and co-promoting activity of the large molecular weight components of aqueous tobacco extracts. Carcinogenesis 1980 1(4) 317-321. 

Hepatic peroxisome proliferation depends on a nuclear receptor, PPARa, to mediate these responses in mice, based on lack of response to peroxisome proliferators in PPARa-deficient mice. In one study with another peroxisome proliferator, WY-14,643, carcinogenesis was shown to be dependent on the same receptor. Oral administration of di(2-ethylhexyl) phthalate failed to elicit markers of peroxisome proliferation in PPARa-deficient mice, while the same treatment elicited this response in normal mice. Metabolites of di(2-ethylhexyl) phthalate caused activation of PPARa-mediated gene expression in mammalian cell co-transfection assays. Differences between responsive rodents and humans in various aspects of PPARa-mediated regulation of gene expression are consistent with the lack of activity of di(2-ethylhexyl) phthalate metabolites in hepatocyte cultures from 12 people studied to date. 

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