Cell culture assays for chemicals with tumor-promoting or tumor-inhibiting activity based on the modulation of intercellular communication

摘要: The ability of chemicals with tumor-promoting or tumor-inhibiting activity to modulate gap junctional intercellular communication is reviewed. two most extensively used types assays for screening tests are (1) metabolic cooperation involving exchange between cells precursors nucleic acid synthesis and (2) dye-transfer that measure fluorescent dye from loaded adjacent cells. About 300 substances different biological activities have been studied using various assays. For tumor promoters/epigenetic carcinogens, a sensitivity 62% 60%. Thirty percent DNA-reactive carcinogens also possess the uncouple complete estimation predictive power these could not be made because majority effectsin vitro yet promoting activityin vivo. Both transfer respond well following classes substances: phorbol esters, organochlorine pesticides, polybrominated biphenyls, promoters urinary bladder, some toxins, peroxisome proliferators, complex mixtures. Results ofin such promoters/nongenotoxic as bile acids, peroxides, alkanes, hormones, mineral dusts, ascorbic acid, okadaic benz(e)pyrene, do correlated data vivo two-stage carcinogenesis. Enhancement was found 18 chemicals. Among these, cAMP, retinoids, carotenoids demonstrated inhibition We examine number factors important routine screening, including requirement biotransformation agents exert effects on junction. discuss mechanisms promoter inhibitor permeability, influences protein kinase activation, changes in proton Ca2+ intracellular concentrations, oxy radical production.