Fatty acid-induced modifications of mouse mammary alveolar lesions in organ culture.
A newly developed adult RIII mouse mammary gland organ culture system was used to examine the effects of fatty acids and a prostaglandin synthase inhibitor on the survival and/or growth of lactogenic hormone-independent mammary alveolar lesions (MAL). The number of MAL per gland that persisted in the absence of lactogenic hormones was increased in cultures treated with arachidonic acid (24.0 +/- 3.4), and was decreased after treatment with stearic acid (4.0 +/- 3.4) or indomethacin (5.0 +/- 0.6). Arachidonic acid also induced higher incorporation of [3H]thymidine into the cellular DNA of MAL containing glands. A comparison of [3H]arachidonic acid uptake into intact (MAL containing) glands and parenchyma-free fat pads revealed a selectively higher incorporation of the labeled fatty acid in the intact glands. Arachidonic acid exposure produced higher cumulative amounts (4.02 ng) of prostaglandin E2 (PGE2) which was significantly inhibited (1.66 ng) by indomethacin (p less than 0.001). In contrast, exposure to stearic acid did not lower PGE2 levels below that of controls. A concomitant increase in MAL number and PGE2 production by arachidonic acid and a decrease in both caused by indomethacin suggest that arachidonic acid conversion to PGE2 may have a facilitative role in the survival of MAL.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D005227:Fatty Acids / Q000633:toxicity*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D011230:Precancerous Conditions / Q000139:chemically induced*; D011453:Prostaglandins / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism
D001095:Arachidonic Acids; D005227:Fatty Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D013936:Thymidine; D007213:Indomethacin