Initiation of carcinogenesis

Denda, A., Sai, K., Tang, Q., Tsujuchi, T., Tsutsumi, M., Amanuwa, T., Murata, Y., Nakoe, D., Maruyama, H., Kurokawa, Y. and Konishi, T. (1991). Induction of 8-hydroxydeoxyguanosine but not initiation of carcinogenesis by redox enzyme modulations with or without menadione in rat liver. Carcinogenesis 12, 719-726. 

The weight of evidence from in vivo and in vitro genetic toxicology tests, in vivo liver function studies, and the two-stage tumor promotion assay is adequate to conclude that chlordecone is a promotor rather than an initiator of carcinogenesis. While the evaluation of mirex in an in vivo tumor promoter... 

Yuspa, S.H. and Morgan, D.L. (1981). Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis, Nature 293, 72. 

Peroxides can play a physiological role in the cell but also mediate processes leading to heart disease and carcinogenesis. Fatty acid peroxidation may also be related to free radical-mediated metabolic activation of carcinogens or drugs, which lead to the initiation of carcinogenesis or cytotoxicity. Modification of membrane function as a consequence of lipid peroxidation includes imcoupling of oxidative phosphorylation... 

Brown-Peterson NJ, Krol RM, Zhu Y, Hawkins WE. 1999. N-nitrosodiethyla-mine initiation of carcinogenesis in Japanese medaka (Oryzias latipes) hepatocellular proliferation, toxicity, and neoplastic lesions resulting from short term, low level exposure. Toxicol. Sci. 50 186-94... 

Williams GM, Iatropoulos MJ, Jeffrey AM, Luo FQ, Wang CX, PittmanB. 1999. Diethylnitrosamine exposure-responses for DNA ethylation, hepatocellular proliferation, and initiation of carcinogenesis in rat liver display non-linearities... 

Test Systems Indicative of Inhibiting the Initiation of Carcinogenesis... 

There are two types of microbial degradation of DMNA (Pathways A and B in Figure 2). One is denitrosation, which produces nitrite and amine. This is a reverse of the process of chemical formation of DMNA (Figure 1), and is presumed to be a main process for removal of DMNA from the environment. The other is demethylation, which produces aldehyde and methyl amine. This reaction is considered as a central paradigm for initiation of carcinogenesis. 

There are two pathways of degradation of DMNA by microbial enzymes and by microsomal P-450. One is denitrosation and the other demethylation. Denitrosation is a mflin microbial process for removal of DMNA from the environment, although its degradation through demethylation also takes place by a methanotroph. The reaction catalyzed by microsomal P-450 can couple with the methylation of DNA, a central paradigm for initiation of carcinogenesis. 

The formation of DNA adducts represent a critical step in the initiation of carcinogenesis (Tan et al. 1993). The abihty of exogenous and partly endogenous (Tan et al. 1994) melatonin to suppress the development of carcinogenic processes suggests that melatonin, as a strong component in the antioxidant system, helps to prevent carcinogenesis (Beyer et al. 1998). 

---