Lipid metabolism and enzyme activities in hormone-dependent and hormone-independent mammary adenocarcinoma in GR mice.

Lipid metabolism in hormone-dependent (HD) GR mouse mammary tumors was compared to that in hormone-independent (HI) tumors and normal mammary tissues. HD tumors, like normal mammary tissue but unlike HI tumors, synthesized medium-chain-length fatty acids (MCFA). However, when treated with hormones (estrone and progesterone), the HI tumors were induced to produce MCFA. The activity of thioesterase II correlated positively with the synthesis of MCFA and was influenced by the hormones administered. The activities of NADP+-linked malate dehydrogenase, citrate lyase, acetyl-CoA carboxylase, and fatty acid synthetase, although lower in tumors than in normal glands, were not different in HD as compared to HI tumors. Whereas the predominating lipids synthesized in normal glands were triglycerides, phospholipids comprised about half of the lipid synthesized in the tumors, with no difference between HD and HI tumors. The conversion of D-[U-14C]glucose to 14CO2 was higher in HD tumors than in HI tumors but increased in HI tumors treated with hormones in vivo. By a comparison of the 14CO2 produced from D-[1-14C]glucose and from D-[6-14C]glucose in the presence and absence of an electron acceptor (methylene blue), it was demonstrated that regeneration of NADP+ from NADPH was a rate-limiting step for the pentose phosphate pathway in the tumors. Hence, while differences in the lipid metabolism can be demonstrated between HD and HI GR mouse mammary tumors, some of the changes are due to the hormone treatment rather than to a specific alteration in the tumor itself.

The effect of prolonged fasting on total lipid synthesis and enzyme activities in the liver of the European eel (Anguilla anguilla).

The extent of fatty acid synthesis from [1-14C]acetate in liver slices was reduced 6-fold when eels were fasted for 1-7 weeks and 20-fold when fasted for 39 weeks; thereafter hepatic lipogenesis seemed to remain constant for up to 95 weeks of fasting. After a 1-3 week fast some hepatic enzyme activities were reduced (acetyl-CoA carboxylase decreased 2-fold and fatty acid synthetase declined 5-fold), while others remained unchanged (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, alpha-glycerol phosphate dehydrogenase as well as malic enzyme and ATP-citrate lyase). The optimum temperature for measuring both total lipid synthesis and lipogenic enzyme activity in eel liver was found to be 30 degrees C.

Acyl specificity in triacylglycerol synthesis by mammary adenocarcinoma R3230AC in Fischer rats.

Activities and acyl specificities of both sn-glycero-3-phosphate and diacylglycerol acyltransferases in microsomal fractions isolated from homogenates of the mammary adenocarcinoma R3230AC carried by Fischer rats were compared to those from normal mammary glands of lactating Fischer rats. Although the neoplasm exhibited lower activities for these two enzyme reactions, the specificities for acyl-CoAs as donors were quite similar to those found in the normal tissue counterpart. Long-chain acyl-CoAs were preferred substrates for the sn-glycero-3-phosphate acyltransferase reaction while acyltransferase with diacylglycerol as acceptor showed much less preference. With both normal and neoplastic tissues, the products of each reaction were the same, i.e., phosphatides with sn-glycero-3-phosphate and triacylglycerol with diacylglycerol as acyl acceptors, respectively. All results support the concept of a non-random distribution of fatty acids in the triacylglycerol of this mammary adenocarcinoma in virgin rats which is the same as that from the normal tissue in lactating animals.

Effect of some fatty acid methyl esters on gastrointestinal carcinogenesis by N-methyl-N-nitro-N-nitrosoguanidine in rats.

Methyl linoleate hydroperoxide (MLHP) and native methyl linoleate (ML) were tested for carcinogenicity toward the gastrointestinal (GI) tract in male specific-pathogen-free outbred Wistar rats. N-Methyl-N-nitro-N-nitrosoguanidine (MNNG) was given in the drinking water in a dose of 20 mg/liter when cocarcinogenic properties of the test substances were to be tested. MLHP and ML were fed by stomach tube and had no effect as complete carcinogens. Given concomitantly with MNNG, ML did not enhance carcinogenesis. MLHP in conjunction with MNNG was the only treatment which, as treatment with MNNG in a dose of 83 mg/liter, led to an increase of GI cancers in animals that died before day 354. Cumulative results after a maximum of 612 days showed a distribution of GI cancers in favor of the glandular stomach only after MLHP was given with MNNG.

Effect of estrogen on metabolism and enzyme activities of mammary adenocarcinoma R3230AC in Fischer rats.

Metabolic characteristics and enzyme activities are reported for a variant line of R3230AC tumor, a long-established, transplantable mammary adenocarcinoma in the Fischer rat. Lipogenic enzyme activities from the variant tumor are generally lower than those reported for early generations of this tumor. In addition, the proportion of the medium-chain-length fatty acids in the lipids of this variant line is lower. In the variant tumor, estrogen treatment of host animals results in a reduction of fatty acid synthesis from both acetate and glucose. The response of the variant tumor to estrogen treatment is similar to that for the normal gland in a virgin rat in that lipogenic enzyme activities are lowered in both normal and neoplastic tissues. These enzymatic activities in early generations of tumor R3230AC were similar to those observed in mammary glands from lactating rather than virgin rats. Since the variant tumor still responds to estrogen treatment by a reduced growth rate, we have inferred that, although it undergoes the same structural differentiation observed in earlier generations, the variant tumor line no longer shows certain biochemical changes associated with the lactational state in the normal gland.

Tissue specificity for the effect of estrogen on lipogenic activity in male and female rats.

Estrogen treatment decreased fatty acid synthetase and acetyl-CoA carboxylase (EC 6.4.1.2) activities and lowered the lipogenic capacity of mammary gland and the hormone-responsive, transplantable mammary adenocarcinoma R3230AC in male and female Fischer rats whereas the activity of these enzymes and the lipogenic capacity were increased in liver. Estrogen increased the activity of thioesterase II, an enzyme which terminates fatty acid synthesis at medium chain lengths, in both normal and neoplastic mammary tissue.

Lipoperoxides in organs of vitamin E deficient rats fed large amounts of highly unsaturated fats.

Rats were fed diets containing 10% cod liver oil with and without a supplement of tocopherol acetate for 32 weeks. The determination of peroxides in lipid extracts of adipose tissue, liver, heart and skeletal muscle by different methods was attempted. High amounts of peroxides were found only in adipose tissue of vitamin E deficient animals. Small values were found in other tissues of both groups. The problem whether the organs contain true lipoperoxides, or some other substances are responsible for the peroxide estimates, is discussed.