Cyclic nucleotides in carcinogenesis: activation of the guanylate cyclase-cyclic GMP system by chemical carcinogens.
The roles of cyclic AMP and cyclic GMP in the control of normal cell growth and the pathogenesis of malignant transformation remain uncertain. Several chemical carcinogens rapidly activate the guanylate cyclase-cyclic GMP systems of human and other mammalian tissues, and probably do so through unique free radical or redox reactions not involved in the physiologic regulation of celluar cyclic GMP. Short-term studies in lymphocytes and colonic mucosa with the N-nitroso carcinogen MNNG have failed to demonstrate a direct relationship between the acute increases in cyclic GMP induced by this agent and stimulation of DNA synthesis. Nevertheless, a role for this early cyclic GMP response in the complex processes by which MNNG and other carcinogenic stimuli of cyclic GMP initiate cell transformation is not excluded by these observations. Alternatively, increases in cyclic GMP could be part of the cellular response to injury and linked to the detoxification of chemical carcinogens or other noxious stimuli, rather than to a direct stimulation of cell proliferation. Resolution of these questions clearly awaits a better understanding of the normal cellular actions of cyclic GMP.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D003106:Colon / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D005753:Gastric Mucosa / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D051381:Rats
D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D004247:DNA; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium