Reversal by vitamin A analogues (retinoids) of hyperplasia induced by N-methyl-N'-nitro-N-nitrosoguanidine in mouse prostate organ cultures.
The antihyperplastic activity of beta-retinoic acid (RA) and nine synthetic analogues (retinoids) was examined in organ cultures of mouse prostate made hyperplastic by treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After 8 or 10 days, when most explants developed hyperplasia, the carcinogen was withdrawn and explants were incubated in control medium and medium containing different concentrations of a retinoid. The antimitotic activity of retinoids was compared with that of RA. Different retinoids produced variable degrees of mitotic inhibition in the hyperplastic prostate epithelium. The methylketo cyclopentenyl and 1-methoxyethyl cyclopentenyl analogues of RA were at least 50-fold more active than RA in reversing MNNG-induced hyperplasia. The trimethylmethoxyphenyl analogue of RA and retinyl methyl ether were significantly more active than RA. Three analogues, N-acetyiretinylamine, retinal acetyl hydrazone, and retinal oxime, were as active as RA. The chlorotrimethylphenyl analogue showed less activity than RA, and alpha-retinyl acetate was completely devoid of mitotic inhibitory activity.
D002455:Cell Division / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000037:antagonists & inhibitors*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009924:Organ Culture Techniques; D011230:Precancerous Conditions / Q000188:drug therapy; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology*
D014801:Vitamin A; D008769:Methylnitronitrosoguanidine; D014212:Tretinoin