INFLUENCE OF DIETARY-FAT AND INDOMETHACIN ON THE GROWTH OF TRANSPLANTABLE MAMMARY-TUMORS IN RATS

Abstract

Studies were designed to determine if treatment with indomethacin influenced the growth of a transplantable, metastatic, rat mammary tumor. Female, Wistar-Furth inbred rats were fed either a standard chow diet or a semipurified diet containing 2, 5, 10, or 20% stripped corn oil. Indomethacin was given in drinking water, and rats consumed between 2.5 and 3.0 mg indomethacin/kg body wt per day. Feeding of diets and initiation of treatment with indomethacin were started when rats were weaned (21 days old) and continued until they were killed. Approximately 5 .times. 103 mammary tumor cells (DMBA-4) were injected into the fat pad of the 6th mammary gland which is adjacent to the right inguinal lymph node. Each dietary/treatment group consisted of at least 10 rats. Since indomethacin inhibits prostaglandin [PG] synthesis, 2 other groups of non-tumor-bearing rats were used to determine if dietary fat and treatment with indomethacin either influenced PGE2 production (in vitro) by mononuclear cells from the spleen or altered serum levels of fatty acids. The rate of tumor growth in untreated rats was significantly greater when the dietary fat content was either 10 or 20% compared to diets containing either 2 or 5% fat; the tumor growth-promoting effects of 10 and 20% fat diets were completely abrogated in rats treated with indomethacin; treatment with indomethacin also inhibited tumor growth in rats fed diets containing either 2 or 5% fat; synthesis of PGE2 by mononuclear cells from the spleens of untreated rats increased as the dietary fat content increased; in indomethacin-treated rats, PGE2 synthesis was inhibited in all dietary groups and was not dependent on dietary fat; and in both untreated and indomethacin-treated rats, the serum concentrations of oleic and linoleic acids were influenced to the same extent by dietary fat.