Anticarcinogenic effects of retinoids in animals.
Retinoids are effective inhibitors of chemical carcinogenesis in the skin, mammary gland, esophagus, respiratory tract, pancreas, and urinary bladder of experimental animals. Modification of the basic retinoid structure has produced retinoids with enhanced target organ specificity, resulting in increased anticancer activity with reduced systemic toxicity. Newer retinoidal benzoic acid derivatives are even more active. Combining retinoid treatment with other modulators of carcinogenesis results in a synergistic inhibition of tumor development. Retinoids in combination with hormonal manipulation are much more effective in inhibiting mammary carcinogenesis than is either treatment alone; this combination approach also inhibits mammary tumor recurrence following surgical removal of the first tumor. Retinoids are most effective when administered shortly after the carcinogenic insult. However, even when retinoid treatment is delayed, the compounds are still effective cancer chemopreventive agents for the mammary gland and urinary bladder. The time that retinoid exposure can be delayed and retain an anticancer effect is directly related to tumor latency, with a longer delay permissible against tumors with long latent periods. The mechanism(s) by which retinoids inhibit carcinogenesis is unknown; however, in the mammary gland, retinoids inhibit differentiation and proliferation, DNA synthesis, and RNA polymerase activity. Cytosolic retinoid-retinoid receptor complexing is apparently a prerequisite for the nuclear interaction of retinoids, at least in mammary cells.
D000818:Animals; D002273:Carcinogens / Q000037:antagonists & inhibitors; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D051381:Rats; D012176:Retinoids / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000517:prevention & control
D002273:Carcinogens; D012176:Retinoids