Cancer Chemical carcinogens

Trauma appears to play an important role in cancer. Any long-lasting wound or sore is considered a potential site for cancer and is thus listed as one of the warning signs. It has been shown that wound healing alone can promote the formation of skin tumors initiated by DMBA (20). As pointed out later in this chapter, inflammation and cellular proliferation are related to chemically induced cancer. Chemical carcinogens and tumor promoters induce inflammation and hyperplasia in mouse skin, but it is also known that not all inflammatory-hyperplastic agents cause skin cancer or promote it (21). 

In additional EPA studies, subchronic inhalation was evaluated ia the rat for 4 and 13 weeks, respectively, and no adverse effects other than nasal irritation were noted. In the above-mentioned NTP chronic toxicity study ia mice, no chronic toxic effects other than those resulting from bronchial irritation were noted. There was no treatment-related increase ia tumors ia male mice, but female mice had a slight increase in bronchial tumors. Neither species had an increase in cancer. Naphthalene showed no biological activity in other chemical carcinogen tests, indicating Htde cancer risk (44). No incidents of chronic effects have been reported as a result of industrial exposure to naphthalene (28,41). 

Cancer is a disorder of the body s control of the growth of cells. For a list of examples of human chemical carcinogens, and the relevant target organs, refer to Table 4.10. 

The involvement of tobacco smoke carcinogens in the aetiology of lung cancer is conclusively established, but the role of specific chemical carcinogens as inducers of colorectal cancer is much less clear. Mutagenic pyrolysis products derived from cooked food have come under suspicion as possible... 

Dunkel VC, Pienta RJ, Sivak A, et al. 1981. Comparative neoplastic transformation responses of Balb/3T-3 cells, Syrian hamster embryo cells, and Rauscher murine leukemia virus-infected Fischer 344 rat embryo cells to chemical carcinogens. J Nat Cancer Inst 67 1303-1315. 

Simmon VF. 1979a. In vitro assays for recombinogenic activity of chemical carcinogens and related compounds with Saccharomyces cerevisiae D3. J Nat Cancer Inst 62 901-909. 

Wattenberg LW. 1975. Effects of dietary constituents on the metabolism of chemical carcinogens. Cancer Res 35(11) 3326—3331. 

IARC (1979). Handling Chemical Carcinogens in the Laboratory Problems of Safety, Scientific Publications No. 33. International Agency for Research on Cancer, Lyons, France. 

Williams, G.M. (1976a). Carcinogen-induced DNA repair in primary rat liver cell cultures a possible screen for chemical carcinogens. Cancer Lett. (Shannon, Ire.) 1 231-236. Williams, G.M. (1976b). The detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures. Cancer Res. 37 1845-1851. 

NOC constitute a large category of genotoxic chemical carcinogens occurring in human diet and are known to induce cancer in experimental animals. Nitrosamines are generally found in foods since they are more stable than nitrosamides. Some NOC precursors do not act directly but must be converted to other nitrosation species. 

It has been proposed that in as many as 70-80% of the cases of human cancer environmental chemicals are the causative factors (JL). There is no reason why similar estimates would not be valid for animals. It is noteworthy that the occurrence of chemical carcinogens is widespread in the aquatic environment. For example, of the PAH s, BP is found in the concentration of 50 to 100 yg/m3 in what is considered moderately polluted surface water in waste water as much as 100,000 yg/m3 has been measured (6l). Several... 

Lee, D.J., Wales, J.H., Ayres, J.L. and Sinnhuber, R.O. Synergism between cyclopropenoid fatty acids and chemical carcinogens in rainbow trout (Salmo gairdneri). Cancer Res. (1968) 28, 2312-2318. 

Milo, G. E., I. Noyes, J. Donahoe, and S. Weisbrode. 1981. Neoplastic transformation of human epithelial cells in vitro after exposure to chemical carcinogens. Cancer Res 41(12 Pt 1 ) 5096—102. 

Maronpot RR, Shimkin MB, Witschi HP, et al. 1986. Strain A mouse pulmonary tumor test results for chemical previously tested in the National Cancer Institute carcinogenicity tests. J Natl Cancer Inst 76 1101-1112. 

Models for determining the dose-response relationship vary based upon the type of toxicological hazard. In the dose-response for chemical carcinogens, it is frequently assumed that no threshold level of exposure (an exposure below which no effects would occur) exists, and, therefore, any level of exposure leads to some finite level of risk. As a practical matter, cancer risks of below one excess cancer per million members of the population exposed (1 x 10 ), when calculated using conservative (risk exaggerating) methods, are considered to represent a reasonable certainty of no harm (Winter and Francis, 1997). 

We shall begin with a little history, and then move to a discussion of cancer statistics and the causes of cancer, and then provide some background on cancer biology and the mechanisms of tumor development. Some of the general characteristics of chemical carcinogens will also be covered. The methods for identifying chemical carcinogens are the subject of Chapter 6. How their risks are estimated is left to later chapters. 

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