Chemical carcinogenesis mechanisms

McCormick, J.J., Silinskas, K.L., and Maher, V.M. (1980). Thinsfonna-tion of diploid human fibroblasts by chemical carcinogens, page 491 in Carcinogenesis, Fundamental Mechanisms and Environmental Effects, Pullman, B. Tso, P.O.P and Gelboin, H., Eds. (D. Reidel Publishing Company, Boston). 

Goldsworthy Chemically induced cell proliferation in carcinogenesis in Mechanisms of carcinogenesis in 27A30... 

At the opening of the 1968 Jerusalem Symposium on Physico-chemical Mechanisms of Carcinogenesis, the Pullmans suggested [10] that the principal (interrelated) problems of controversy were ... 

A. Pullman and B. Pullman, in Physico-Chemical Mechanisms of Carcinogenesis, eds. E.D. Bergmann and B. Pullman (Israel Academy of Sciences and Humanities, Jerusalem, 1969) p. 9. 

L.C. Cusachs and R.H. Steel, in Physico-chemical Mechanisms of Carcinogenesis, ed. 

Experimental animal studies have played a key role in the understanding of the mechanisms of chemical carcinogenesis. The duration of development of a cancer in humans may be several decades, and the development probably includes several steps. Furthermore, individual susceptibility is also important for the disease. Therefore, it has been extremely difficult to make the required observations in exposed individuals. 

Fubini, B., Bolis, V., Giamello, E. and Volante, M. (1991). Chemical functionalities at the broken fibre surface relatable to free radicals production. In Mechanisms in Fibre Carcinogenesis (eds. R.C. Brown, J.A. Hoskins and N.F. Johnson) pp. 415-432. Plenum, New York. 

The reaction of metabolically generated polycyclic aromatic diol epoxides with DNA Ua vivo is believed to be an important and critical event in chemical carcinogenesis Cl,2). In recent years, much attention has been devoted to studies of diol epoxide-nucleic acid interactions in aqueous model systems. The most widely studied reactive intermediate is benzo(a)pyrene-7,8-diol-9,10-epoxide (BaPDE), which is the ultimate biologically active metabolite of the well known and ubiquitous environmental pollutant benzo(a)pyrene. There are four different stereoisomers of BaPDE (Figure 1) which are characterized by differences in biological activities, and reactivities with DNA (2-4). In this review, emphasis is placed on studies of reaction mechanisms of BPDE and related compounds with DNA, and the structures of the adducts formed. 

Areas in which additional information is still needed relates to the role and relative importance of different adducts and the mechanisms by which they initiate cells. General principles are developing which will allow better predictions to be made at each of the stages of chemical carcinogenesis outlined in Table I. The ultimate goal therefore, would be, by a combined analysis of all these steps, to predict accurately the carcinogenicity of newly discovered or untested PAH derivatives. 

Barrett JC, Huff J. 1991. Cellular and molecular mechanisms of chemically induced renal carcinogenesis. Renal Failure 13 211-225. 

The mechanisms and theories of chemical carcinogenesis are as follows (Powell and Berry, 2000 Williams and Iatropoulos, 2001) ... 

A review of data from 250 chemicals found an 82% concordance between results of carcinogenicity testing in the mouse and the rat (Purchase, 1980). Haseman et al. (1984a) reported a concordance of 73% for 60 compounds studies in both species. However, 30 to 40% of 186 National Cancer Institute (NCI) chemicals were found to be positive in one species and negative in the other (Gold et al., 1984). It is reasonable to conclude that neither rodent species will always predict the results in the other rodent species or in humans, and that the use of two species will continue until we have a much better understanding of the mechanisms of carcinogenesis. 

Considering the relevance of aza-PAHs in the elucidation of the mechanism of chemical carcinogenesis, our goal was to apply DFT methods to achieve a better understanding of the structural and electronic factors affecting the reactivity of this type of compounds. In this chapter we summarize our recent and ongoing computational studies in this field. 

Williams GM. 1981. Liver carcinogenesis The role for some chemicals of an epigenetic mechanisms of liver-tumor promotion involving modification of the cell membrane. Food Cosmet Toxicol 19(5) 577- 583. 

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