Affiliations: National Food Safety and Toxicology Center, Department
of Pediatrics and Human Development, Michigan State University, East Lansing,
MI 48824, USA
Note: [] 246 National Food Safety and Toxicology Center, Dept. Pediatrics
and Human Development, Michigan State University, East Lansing, Michigan 48824.
Tel.: +1 517 353 6346; Fax: +1 517 432 6340; E-mail: trosko@msu.edu
Abstract: Chemopreventive or chemotherapeutic agents have been those that
either kill cancer cells to a differential degree over the non-cancer cells or
those chemicals that either block the induction of tumors in carcinogen-treated
animals or retard transplanted tumors in animals. Carcinogenesis is a
multi-stage, multi-mechanism process, involving the irreversible alteration of
a stem cell (``initiation''), followed by the clonal proliferation of the
initiated cell (``promotion''). To develop a strategy for intervention with
chemoprevention/chemotherapeutic chemicals, the basic mechanism(s) of
carcinogenesis must be understood. Gap junction intercellular communication
(GJIC) regulates cell growth, differentiation, apoptosis and adaptive functions
of differentiated cells. Normal cells have functional GJIC while cancer cells
do not. Tumor promoters and oncogenes inhibit GJIC, while anti-tumor promoter
and anti-oncogene drugs can reverse the down-regulation of GJIC. Transfection
of gap junction genes (connexins) has been shown to reverse the tumorigenic
phenotype. If prevention/treatment of cancer is to occur, prevention of the
chronic down regulation of GJIC by tumor promoters in non-tumorigenic but
initiated cells or the up-regulation of GJIC in stably down-regulated GJIC in
tumor cells must occur to prevent or to treat cancers.
Keywords: gap junctions, connexins, anti-promoters, chemoprevention
Journal: BioFactors, vol. 12, no. 1-4, pp. 259-263, 2000
