Carcinogenesis chemical initiators

Cancer chemoprevention refers to the administration of chemical agents to prevent the initiational (mutational) and promotional events that occur during the process of neoplastic development (carcinogenesis). The initiation involves the direct action of the carcinogen on target cells (or after his metabolic activation) whereas promotion and/ or progression means that the initiated cells are stimulated to proliferate. 

A mutagen is a chemical that can induce alterations in the DNA. Mutations occurring in germ cells are inheritable and may lead to genetic diseases. If mutations take place in somatic cells, carcinogenesis may be initiated. 

Several chemicals can act as initiators and/or promoting agents participating actively in the process of carcinogenesis and also producing synergistic effects when taken simultaneously via multiple routes of exposure. 

Carcinogenesis develops in three stages initiation, promotion, and progression. Chem-ical substances can act at the initiation stage or at the promotion stage. Moreover, some chemicals have both initiating and promoting activities. 

Hradec J, Spiegelhalder B, Preussmann R. 1988. The initiator tRNA acceptance assay as a shortterm test for carcinogens. 2. Results with ten compounds selected by the International Programme on Chemical Safety for the evaluation of short-term tests for carcinogens. Carcinogenesis 9 843-846. 

In contrast, promotion is reversible to some extent, and it is only effective following, not preceding, the initiating events. These discoveries suggest that only the initiation stage of carcinogenesis has an absolute requirement for the chemical carcinogen. 

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. 

Moller L, Torndal UB, Eriksson LC, et al. 1989. The air pollutant 2-nitrofuran as initiator and promoter in a liver model for chemical carcinogenesis. Carcinogenesis 10(3) 435-440. 

N-nitrosodialkylamines - nitrosamines - constitute one of the most extensive series of known chemical carcinogens. Most nitrosamines can initiate tumors in at least one animal species, and all animal species which have so far been tested are susceptible to nitrosamine carcinogenesis O, 2 ). 

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