Influence of thiols and inhibitors of prostaglandin biosynthesis on the carcinogen-induced development of mammary lesions in vitro.
Mouse mammary gland undergoes physiological changes, comparable to that in the animal, under appropriate hormonal conditions in organ culture. Moreover, they form mammary lesions when exposed to the carcinogen, dimethylbenz(a)anthracene (DMBA) for a short duration. This organ culture system was utilized in the present of study to evaluate activity of two groups of potential chemopreventive agents. Activity of inhibitors of prostaglandin synthesis and thiols was determined at five concentrations. The average incidence of mammary lesions induced by DMBA was 60%, oltipraz oxithiazolidine, thioctic acid and N-acetylcysteine were effective at different concentrations, whereas diallyldisulfide, sulfasalazine and ajoene were marginally effective. Within the inhibitors of prostaglandin synthesis category, aspirin, ibuprofen and indomethacin were effective, whereas dipyridamol, piroxicam and pentoxyphyllin were ineffective. The results correlated well with the known in vivo effects of these agents on chemically induced carcinogenesis of mammary gland. The study provides evidence for the use of mammary gland organ culture as a screening total system for prediction of effective chemopreventive agents against mammary carcinogenesis.
Mehta
R G
RG
Life Sciences Department, IIT Research Institute, Chicago, IL 60616.
Steele
V
V
Kelloff
G J
GJ
Moon
R C
RC
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004176:Dipyridamole / Q000494:pharmacology; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D010431:Pentoxifylline / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D011448:Prostaglandin Antagonists; D013438:Sulfhydryl Compounds; D010894:Piroxicam; D015127:9,10-Dimethyl-1,2-benzanthracene; D004176:Dipyridamole; D001241:Aspirin; D010431:Pentoxifylline; D007052:Ibuprofen; D007213:Indomethacin