Carcinogenesis process

In spite of the intrinsic complexity of the carcinogenesis process, QSAR models can be generated successfully for individual classes of congeneric chemicals. Crucial requirements are (a) the class is well defined (truly congeneric, with the same mechanism of action), and (b) a statistically sufficient number of compounds with measured biological activity exists. 

Cancer prevention is now one of the most urgent projects in public health. It is evident that an understanding of the mechanisms of the carcinogenesis process is essential for cancer chemoprevention. Most cancer prevention research is based on the concept of multistage carcinogenesis initiation —> promotion — progression [2-4] [Fig. (1)]. Cancer chemoprevention is defined as the use of specific natural and... 

Finally, a third approach has been proposed with five stages that focus on the chemical structure, DNA-reactivity, epigenetic effects, limited bioassays, and finally, the application of accelerated bioassays. These accelerated bio assays require 40 weeks and apply to the use of sensitive markers for induction of neoplasia in comparison to positive control compounds for important organs in human carcinogenesis. It enables data acquisition of the entire carcinogenesis process directed toward developing mechanistic information. This system would have the potential to replace the chronic bioassay in rodents in some circumstances and could serve a analternative to a chronic bioassay in a second species. ... 

Laboratory fish models of carcinogenesis complement and attempt to provide an explanation for observations made in the field. Historically, the fish species selected for such studies differ in the lab, small domestic freshwater fish are opted for in the held, estuarine species living in close association with contaminated sediments are selected. Extrapolating across species has its limits, though it has nevertheless been possible to determine much of the universal mechanisms relating to the carcinogenesis process in fish species. 

Studies in animal models have demonstrated that tea polyphenols can inhibit carcinogenesis at all stages, including initiation, promotion, and progression. This multifaceted inhibition of carcinogenesis process is attributed to a combination of antioxidative, antiproliferative, and proapoptotic effects of these polyphenols. Tea polyphenols have also been shown to inhibit the processes of angiogenesis, tumor metastasis, and invasion in animal models. ... 

The RER+ carcinogenesis process is thus divided up into two clearly distinct evolutive phases (1) a preliminary phase concerning normal or nearly normal cells in which the acquired mutations necessary to initiate a RER+ carcinogenesis are paradoxically counterselected mainly because of apoptosis and possibly because of senescence and (2) an explosive phase that takes place when the RER hypermutator state is no longer counterselective. 

An important determinant of whether or not a cell becomes initiated by a chemical carcinogen is DNA repair. Inhibition of the excision repair system allows a greater chance that the carcinogenic damage will not be repaired, thus leading to the irreversible initiated carcinogenic state (1). Likewise, inhibition or induction of error prone DNA repair could lead to a drastic modification of the carcinogenesis process (1). 

Another interesting finding is the possible effect of l,25-(OH)2l>2 on the carcinogenesis process of skin. The compound is reported to suppress papilloma development in skin Induced by agents such as methylcholanthrene and promoters such as phorbol esters 13 however,... 

Apoptosis is a major mechanism by which many current synthetic anticancer and chemotherapeutic agents induce their effect. As such, apoptosis has emerged as an important mechanism by which dietary compounds may exhibit chemopreventive potential. Apoptosis may remove cells undergoing neoplastic transformation when other cellular defense systems have failed to block the carcinogenesis process upstream. Removing the neoplastic cells by induction of apoptosis represents a cornerstone of the chemopreventive paradigm [134]. 

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