Fatty acid-induced modifications of mouse mammary alveolar lesions in organ culture

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Abstract
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 add (4.0 ± 3.4) or indomethadn (5.0 ± 0.6). Arachidonic add also induced higher incorporation of [ 3 H]thymidine into the cellular DNA of MAL containing glands. A comparison of [ 3 H]arachidonic add uptake into intact (MAL containing) glands and parenchymafree fat pads revealed a selectively higher incorporation of the labeled fatty add in the intact glands. Arachdionk add exposure produced higher cumulative amounts (4.02 ng) of prostaglandin E 2 (PGE 2 ) which was significantly Inhibited (1.66 ng) by indomethacin (p2 levels below that of controls. A concomitant increase in MAL number and PGE 2 production by arachidonic add and a decrease in both caused by indomethacin suggest that arachidonic add conversion to PGE 2 may have a facilitative role in the survival of MAL.