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)