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Chemical carcinogenesis.

Authors
Weston-A; Harris-CC
Source
Cancer Medicine 5th Edition, Hamilton, Ontario, Canada: BC Decker, Inc., 2000 Jan; :185-194
Link
NIOSHTIC No.
20021091
Abstract
Chemical carcinogenesis is a multi-stage process that begins with exposure, usually to complex mixtures of chemicals that are found in the human environment (Table 12.1). 1-3 Once internationalized, carcinogens frequently are subjected to competing metabolic pathways of activation and detoxication, although some reactive environmental chemicals can act directly. Variations among individuals in the metabolism of carcinogens, together with differences in DNA-repair capacity and response to tumor promoters, govern the relative risk of an individual. 4 The initial genetic change that occurs as the result of chemical-DNA interaction is termed tumor inhibition. Thus, initiated cells are irreversibly altered and are at greater risk of malignant conversion that are normal cells. The epigenetic effects of tumor promoters facilitate the clonal expansion of the initiated cell. 5 This selective, clonal growth advantage results in the formation of a focus of preneoplastic cells. These cells are more vulnerable to progress toward tumorigenesis because they present a larger, more rapidly proliferating target population for the further action of chemical carcinogens, oncogenic viruses, and other cofactors. Additional genetic changes occur, and consequently, the accumulation of mutations, which may activate protooncogenes and inactivate tumor-suppressor genes, leads to malignant conversion, tumor progression, and metastasis. The underlying genetic mechanisms that regulate chemical carcinogenesis are becoming increasingly well understood, and the insights generated have assisted in the development of methodologies designed to assess human cancer risk and susceptibility factors. The results of these latter studies are further intended to mold strategies for cancer prevention.
Keywords
Carcinogenesis; Carcinogenicity; Carcinogens; Exposure-assessment; Genetic-factors; Genetics; Risk-analysis; Risk-factors; Tumorigens; Tumorigenesis; Tumors; Cancer; Occupational-exposure; Exposure-levels; Environmental-factors; Tobacco-smoke; Lung-cancer; Bladder-cancer
Publication Date
20000101
Document Type
Book or book chapter
Editors
Bast-RC; Kufe-DW; Pollock-RE; Weichselbaum-RR; Holland-JF; Frei-E
Fiscal Year
2000
NTIS Accession No.
NTIS Price
ISBN No.
1550091131
NIOSH Division
HELD
Source Name
Cancer Medicine 5th Edition
State
WV
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