Reversal by vitamin A analogues (retinoids) of hyperplasia induced by N-methyl-N'-nitro-N-nitrosoguanidine in mouse prostate organ cultures.

Abstract

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 After 8 or 10 days, when most explants developed hyperplasia, the carcinogen was withdrawn and explants were incubated in control medium and medium containing different concentrations of a retinoid.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.

• Authors: D P Chopra, L J Wilkoff
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 58 Issue 4 Pg. 923-30 (Apr 1977) ISSN: 0027-8874 [Print] United States
• PMID: 557570 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Vitamin A
• Methylnitronitrosoguanidine
• Tretinoin

Topics

• Cell Division (drug effects)
• Epithelium (drug effects, pathology)
• Hyperplasia (chemically induced)
• Male
• Methylnitronitrosoguanidine (antagonists & inhibitors)
• Neoplasms, Experimental (drug therapy)
• Organ Culture Techniques
• Precancerous Conditions (drug therapy)
• Prostate (drug effects, pathology)
• Prostatic Neoplasms (drug therapy)
• Structure-Activity Relationship
• Tretinoin (pharmacology)
• Vitamin A (analogs & derivatives, pharmacology)