Aspects of Carcinogenesis

Altered requirements arise for maintenance / of homeodynamic equilibrium. 

Both l -cells and normal cells undergo hyperplasia hypertrophy Tumor promoters, like TPA or phenobarbital, cause the mitotic binomial expansion of the T-cells which goes from a few l -cells to a substantial set of altered-colonies within the local syncytium of cells in the exposed organ. 

Colonies form with distinct, bazzare, or plus-growth characteristics. 

Interaction of colonies and differential competition for nutrients. Qentotoxic events occur in DMA, in 

Electrolyte and pH gradients become adversely affected. Because of paucity of ATP de novo vascularization occurs. More cells accumulate with unrepaired mutations in T-cells which become more Independent of LTA showing a loss of cellular architecture in preneoplastic tumors. An reversibly malignant transition occurs I - I cells. 

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This book is expected to be of interest to investigators active in all aspects of carcinogenesis research as well as to graduate students, educators, and others seeking an introduction to this important field of research. 

JULL, J.W. (1976). Endocrine aspects of carcinogenesis, page 52 in Chemical Carcinogens, Searle, C.E., Ed. (American Chemical Sodety, Washington). 

Liotta, L. A., Cancer cell invasion and metastasis. Sci. Am. 266 54-63, 1992. A most important aspect of carcinogenesis that we did not deal with in our short supplement. 

Lu, F.C. 1979. Assessments at an international level of health hazards to man of chemicals shown to be carcinogenic in laboratory animals. Pp. 315-328 in Regulatory Aspects of Carcinogenesis, F. Coulston, ed. New York Academic Press. 

Kolbye, A.C, Jr., Decision-making Issues Relevant to Cancer Inducing Substances. In "Regulatory Aspects of Carcinogenesis and Food Additives The Delaney Clause" (Coulston ... 

Coulston, F. (ed.) (1979) Regulatory Aspects of Carcinogenesis and Food Additives the Delany Clause, New York Academic Press. 

Sung and Lazar [173], and Birks [82] depend on a parabolic rather than a linear fit of the data (as mentioned in Section 3.2) and may still apply for restricted systems indeed, some such limitation applies to theories on most aspects of carcinogenesis. Thus Cammerata, Yau and Rogers [175] presented relations between ionization potentials—molecular polarizabilities and partition coefficients. The inference of a link between solubility theories and MO indices is not unexpected in view of the influence of molecular polarizability on dispersion-attraction interaction energies in solution. An approximate, though rather less relevant, inverse dependence of ionization potential on polarizability has been noted [176]. 

It does suggest, however, that our original assumptions concerning d were at least reasonable. In addition, the dose-depen-dent model can be manipulated to examine - in a general sense -some aspects of interspecies variations in susceptibility to nitrosamine carcinogenesis. 

Lijinsky, W. and D. Schmal. 1978. Carcinogenesis by nitroso derivatives of methylcarbamate insecticides and other nitrosoamides in rats and mice. Pages 495-501 in E.A. Walker, M. Castenegro, L. Griciute, and R.E. Lyle (eds.). Environmental Aspects of N-nitroso Compounds. World Health Qrg., Int. Agency Res. Cancer, IARC Sci. Publ. 19. 

Bowden, G.T., D. Jaffe, and K. Andrews. 1990. Biological and molecular aspects of radiation carcinogenesis in mouse skin. Radiation Res. 121 235-241. 

In the experimental evaluation of substances for carcinogenesis based on experimental results of studies in a nonhuman species at some relatively high dose or exposure level, an attempt is made to predict the occurrence and level of tumorogenesis in humans at much lower levels. In this chapter we will examine the assumptions involved in this undertaking and review the aspects of design and interpretation of traditional long-term (lifetime) animal carcinogenicity studies as well as some alternative short-term models. 

It is not known how chemicals cause cancer. A fascinating aspect of the story is that many "carcinogenic" chemicals are in fact, not the culprits responsible for cancer induction. The metabolic processes of the body change the chemicals from relatively innocuous substances into reactive intermediates which in as yet unknown fashion, trigger the chain of events which finally result in tumor formation. In other words, chemical carcinogenesis is an effect of "failed" detoxification. 

Quantitative Aspects of Exposure and Mechanism in A Nitrosamine Carcinogenesis... 

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. 

Upton, A.C. (1984). Biological aspects of radiation carcinogenesis, page 9 in Radiation Carcinogenesis Epidemiology and Biological Significance, BOICE, J.D., Jr. and Fraumeni, J.F., Jr., Eds. (Raven Press, New York). 

Brookes P. Quantitative aspects of the reaction of some carcinogens with nucleic acids and the possible significance of such reactions in the process of carcinogenesis. Cancer Res 1966 26 1994-2003. 

Stanley LA. Molecular aspects of chemical carcinogenesis The role of oncogenes and tumour suppressor genes. Toxicology 1995 96 173. 

Although cancer is known to occur in many groups of animals, the primary interest and the focus of most research is in human cancer. Nevertheless, much of the mechanistic research and the hazard assessment is carried out in experimental animals. A consideration of the general aspects of human carcinogenesis follows. 

Figure 12.10 General aspects of chemically induced carcinogenesis.

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