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Apoptosis and Chemical Carcinogenesis
Author(s) -
Marsman Daniel S.,
Barrett J. Carl
Publication year - 1994
Publication title -
risk analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 130
eISSN - 1539-6924
pISSN - 0272-4332
DOI - 10.1111/j.1539-6924.1994.tb00247.x
Subject(s) - carcinogenesis , apoptosis , programmed cell death , biology , cell growth , microbiology and biotechnology , cell , population , neoplastic cell , cell cycle , cell division , cancer research , chemistry , biochemistry , cancer , genetics , medicine , environmental health
Long recognized as a normal component of organogenesis during development, apoptosis (programmed cell death) has recently been implicated in alterations of cell growth and differentiation. Tissue homeostasis is normally maintained by a balance between cell division and cell death, with apoptosis often functioning in complement to cell growth. Thus, antithetical parallels in chemical carcinogenesis can be drawn between apoptosis and the proliferative events more commonly addressed. While enhanced cell replication may contribute to an increased frequency of mutation, apoptosis within a tissue may counteract chemical carcinogenesis through loss of mutated cells. Many strong carcinogens act as tumor promoters, selectively expanding an initiated cell population advantageously over surrounding cells. Similarly, chemicals with a selective inhibition of apoptosis within an initiated population would offer a growth advantage. In contrast, chemicals causing selective apoptosis of initiated cells would be expected to have an anticarcinogenic effect. Selective apoptosis, in concert with cell‐specific replication, may explain the unique promoting effects of different carcinogens such as the peroxisome‐proliferating chemicals, phenobarbital, and 2,3,7,8‐tetrachloro‐dibenzo‐ p ‐dioxin (TCDD). Cell turnover, both cell growth and cell death, is central to the process of chemically induced carcinogenesis in animals and understanding its impact is a critical determinant of the relevance of chemically induced effects to man.