Potential Indirect Mechanisms of Carcinogenesis. A Preliminary Taxonomy.
NIOSH 1986 Feb:92 pages
A preliminary taxonomy of possible indirect mechanisms by which chemicals might increase the incidence of tumors was presented. An attempt was made to determine the expected shapes of dose response relationships for agents acting by the different processes. Indirect processes that can increase the frequency of observed tumors were listed including changes in basic transport processes, changes in metabolic processing, changes in the effective amount of target DNA for reaction, and changes in the efficiency of repair of initial DNA lesions. Indirect processes that alter the frequency with which initiated cells progress through subsequent stages in the carcinogenic process were discussed, including the induction of subsequent genetic changes along the pathway to carcinogenesis, changes in the removal of initiated cells by terminal differentiation, the release of initiated cells from growth control by neighboring cells, and changes in the rates of proliferation or survival of initiated cells relative to the proliferation of normal cells. Indirect processes that might change the survival, growth, and spread of tumors or the progression of tumors included changes in hormonally mediated processes that speed up growth of specific cell types, changes in the efficiency of immune surveillance, and changes in local tissue conditions that favor colonization of new tissues by metastases.
Carcinogenesis; Tumorigenesis; Molecular-biology; Teratogenesis; Nucleic-acids; Azo-compounds; Nitrosamines; Laboratory-animals; Liver-cancer; Bladder-cancer; Breast-cancer; Skin-disorders;
NTIS Accession No.
Center for Technology, Policy and Industrial Development, Massachusetts Institute of Technology, Cambridge, Massachusetts, Report No. CTPID 86-3, NIOSH Cooperative Agreement No. U60/CCU100929-01, 92 pages, 91 references