Retinoids and cancer prevention.
As indicated above, in some cases the effects of retinoids appear to be species-specific. Although retinyl acetate and 4-HPR are ineffective in preventing mammary cancer induced by DMBA or occurring spontaneously in mice, these retinoids prevent carcinogen-induced mammary cancer in rats. In contrast, retinoids have modest chemopreventive activity for bladder cancer in various strains of both mice and rats and may have some therapeutic and preventive effects in human bladder. Retinyl palmitate is reported to reduce the incidence of esophageal lesions in hamsters; however, retinyl acetate may increase the incidence of esophageal tumors in rats. Although 13-cis-RA reduces the incidence of spontaneous thymic lymphomas in AKR mice and C57Bl/10W mice exposed to X rays and has some therapeutic effect on myelodysplastic syndromes in humans, 4-HPR may enhance leukemic progression in patients with this syndrome. For treatment of this syndrome, selection of the proper retinoid appears to be important. Topically applied retinyl palmitate reduces the incidence of cervical cancer in hamsters, and topically applied RA has a therapeutic effect on cervical dysplasia in humans. Retinamides have a modest chemopreventive effect against pancreatic cancer in rats dosed with azaserine; these compounds are reported both to increase and to decrease the incidence of pancreatic cancer in hamsters. Retinoids may, or may not, be carcinogen-specific in different species. Some are effective in preventing mammary cancer in rats, regardless of which carcinogen is used. Applied to mouse skin, retinoids are active with either DMBA or BP as the carcinogen and 12-tetradecanoyl phorbol-13-acetate (TPA) as the promoter. Nevertheless, retinoids are not effective in preventing skin papillomas and carcinomas caused by UV light. There is no comparable system for humans, although retinoids demonstrate activity against basal cell carcinomas, squamous cell carcinomas, and actinic keratoses on the skin of humans. Fewer bladder tumors develop in rats dosed with HO-BBN when they are put on diets containing certain retinoids, but those dosed with FANFT are not affected. Similarly, retinyl acetate is reported to be active against liver tumors induced by 3'-MeDAB but not against those induced by aflatoxin B1. In contrast, forestomach carcinomas induced in hamsters by either DMBA or BP are prevented by retinyl palmitate. The route of administration of retinoids may also be important.(ABSTRACT TRUNCATED AT 400 WORDS)
Hill
D L
DL
Biochemistry Research, Southern Research Institute, Birmingham, Alabama 35255.
Grubbs
C J
CJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000517:prevention & control; D012176:Retinoids / Q000008:administration & dosage / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D012176:Retinoids