Long-term exposure to elevated levels of circulating TIMP-1 but not mammary TIMP-1 suppresses growth of mammary carcinomas in transgenic mice.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates matrix metalloproteinase activity, acts as a growth stimulator and inhibits apoptosis. We developed transgenic mice to evaluate the relevance of circulating versus mammary TIMP-1 in mammary carcinogenesis. The transgene was placed under the control of the albumin (Alb) promoter for the production of large amounts of TIMP-1 in the liver and release into the systemic circulation to achieve chronically elevated blood levels.

cis-hydroxyproline stimulates the growth of rat mammary carcinoma cells.

With the ever-increasing evidence that the extracellular matrix (ECM) can stimulate tumor growth, it follows that inhibiting the synthesis of tumor-derived stroma may be a potential therapeutic target of cancer progression. The proline analog cis-hydroxyproline (CHP), an inhibitor of collagen deposition, was examined for its effects on the growth of clonal tumor cells that differentially produce type IV collagen and laminin. Two separate clones derived from rat mammary carcinoma cells that produce high and low amounts of type IV collagen and laminin were injected into the flanks of nude mice.

Chronic energy restriction versus energy cycling and mammary tumor promotion.

Chronic energy restriction significantly inhibits mammary tumor promotion in rodents. The present work studied the effect of short-term, intermittent energy restriction or energy cycling on mammary tumor promotion since this feeding paradigm mimics the dieting habits of humans. Female Sprague-Dawley rats were given 7,12-dimethylbenz[a]anthracene (DMBA) at 50 days of age (5 mg ig).

Failure of high fat diets to promote mammary cancers in spontaneously hypertensive rats.

Rat strains differ in their susceptibilities to chemically-induced mammary carcinogenesis. The present study tested the hypothesis that the spontaneously hypertensive rat (SHR) strain is resistant to mammary carcinogenesis. Resistance would imply the presence of the mammary carcinoma suppressor (MCS) gene.

High fish oil diet increases oxidative stress potential in mammary gland of spontaneously hypertensive rats.

1. The purpose of this study was to determine whether high omega-3 (19% menhaden oil, 1% corn oil) or high omega-6 (20% corn oil) fatty acid diets would decrease expression of hypertension in the female spontaneously hypertensive rat (SHR), promote tumourigenesis in the rat 7,12-dimethylbenz[a]anthracene (DMBA) model of mammary cancer or increase the susceptibility of the mammary gland to lipid peroxidation. A group of rats on a 5% corn oil diet served as the low fat control group.

The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats.

Chronic caloric restriction has been shown to inhibit mammary tumor promotion in the 7,12-dimethyl-benz[a]anthracene (DMBA) rat mammary tumor model. The objectives of this study were to determine (i) the effects of chronic caloric cycling (yo-yo dieting) on mammary tumor promotion by high fat diets and (ii) the effect of three dietary regimens +/- superimposed mammary tumor burden on plasma endothelin-1,2 (ET) levels. Female Sprague-Dawley rats were treated with DMBA (5 mg/rat) and divided into three dietary groups: ad libitum (AL) (containing 15% corn oil); 40% calorie restricted (CR) (containing 20% corn oil so consumption of fat was equivalent between AL and CR); a calorie cycled (CC) group fed alternatively AL and CR diets each 48 h period.

Long-term feeding of corn oil, beef tallow, or menhaden oil and eicosanoid levels in BHE/cdb rats.

The effects of long-term feeding of 2 or 10% fat diets containing corn oil, beef tallow, or menhaden oil on the levels of eicosanoids in brain, plasma, and kidney medulla were studied. Male BHE/cdb rats, which carry a genetic trait for non-insulin-dependent diabetes mellitus, were fed these diets for 9 mo, at which time their glucose tolerance levels were determined, as were brain, kidney medulla, and plasma levels of PGE2, 6-keto-PGF1 alpha, and LTB4. Glucose tolerance was abnormal in the 2 and 10% corn oil groups and normal in the 10% menhaden oil groups.

Eicosanoid synthesis and ornithine decarboxylase activity in mammary tumors of rats fed varying levels and types of N-3 and/or N-6 fatty acids.

Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10 mg dose of 7,12-dimethylbenz(a) anthracene (DMBA). Three weeks later they were placed on diets containing either 20% corn oil (CO), 20% primrose oil (PO), 20% black currant seed oil (BCO), 20% borage oil (BO), 15% menhaden oil plus 5% corn oil (15% MO + 5% CO), 10% menhaden oil plus 10% corn oil (10% MO + 10% CO), 5% menhaden oil plus 15% corn oil (5% MO + 15% CO) or 10% menhaden oil plus 10% borage oil (10% MO + 10% BO). Incidences of mammary tumors at 16 weeks post-DMBA were 80% in rats fed the CO diet, 84% in rats fed PO diet, 67% in rats fed BCO diet, 88% in rats fed BO diet, 60% in rats fed 15% MO + 5% CO diet, 67% in rats fed 10% MO + 10% CO diet, 83% in rats fed 5% MO + 15% CO diet, and 92% in rats fed 10% MO + 10% BO diet.

Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets.

Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10-mg dose of 7,12-dimethylbenz(a)anthracene (DMBA). Twenty-one days later they were placed on diets containing either 20% corn oil (CO), 15% menhaden oil plus 5% corn oil (MO + CO), 20% CO plus 0.5% w/w of the irreversible ornithine decarboxylase inhibitor, D,L-2-difluoromethylornithine (CO + DFMO), 20% CO plus 0.

Eicosanoid synthesis in 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in Sprague-Dawley rats fed primrose oil, menhaden oil or corn oil diet.

The comparative effects of high-fat diets (20%, w/w) on eicosanoid synthesis during mammary tumor promotion in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats were studied using diets containing 20% primrose oil (PO), 20% menhaden oil (MO) or 20% corn oil (CO). Sprague-Dawley rats fed the PO or MO diet had 21% of 24% fewer adenocarcinomas, respectively, than rats fed the CO diet. Histologically (i.

Effect of 7,12-dimethylbenz(a)anthracene administration on hepatic drug metabolizing enzymes in female rats fed corn, primrose, and menhaden oils.

Female rats receiving a diet containing 20% menhaden oil beginning at 10 weeks of age and continuing for 13 weeks had hepatic benzo(a)pyrene [B(a)P] hydroxylase activity significantly higher than similar rats fed diets containing 20% corn oil or 20% oil of evening primrose. Compared to microsomes recovered from rats fed the corn oil diet, a significant increase in microsomal cytochrome P-450 content along with an increase in the activity of cytochrome P-450 mediated ethoxycoumarin O-dealkylase was evident in rats fed menhaden oil. Glutathione S-transferase activity of the cytosol of hepatocytes was increased twofold by the feeding of 20% menhaden oil, compared with the feeding of corn or primrose oil.

Effects of dietary primrose oil on mammary tumorigenesis induced by 7,12-dimethylbenz(a)anthracene.

The mammary tumor-promoting effect of a high-fat diet containing 20% evening primrose oil (PO) was compared to that of a 20% corn oil (CO) diet. Mammary tumors were induced in female Sprague-Dawley rats using 10 mg (Study 1) and 5 mg (Study 2) 7,12-dimethylbenz(a)anthracene (DMBA). The 10 mg dose of DMBA gave a total mammary tumor incidence of 47% in rats fed the PO diet and 80% for those fed the CO diet.

Effect of thiamin deprivation on the in vitro metabolic activation of benzo(a)pyrene.

Feeding a thiamin-deficient diet to male and female rats for 3 weeks alters the mixed function oxidases responsible for metabolizing benzo(a)pyrene and enhances the response of these enzymes to induction by phenobarbital or 3-methylcholanthrene. The caloric restriction observed in thiamin deprivation may be partially responsible for the enhanced metabolism in this condition but, as established in pair-feeding studies, was not responsible for the enhanced response to enzyme inducers seen in these animals. The degree of altered response was also seen to depend on the sex of the rat and on the substrate concentration of the incubation mixture.

The effects of dietary corn oil on the metabolism and mutagenic activation on N-nitrosodimethylamine (DMN) by hepatic microsomes from male and female rats.

Microsomes from male and female rats fed a diet containing 10% corn oil metabolized N-nitrosodimethylamine (DMN) more rapidly than microsomes from rats fed a similar diet devoid of corn oil. The daily administration of phenobarbital for 4 days prior to harvesting the microsomes resulted in significant induction of the Vmax for N-demethylation of DMN in rats fed the fat-free diet but resulted in no induction (females) or suppression (males) of this enzyme in rats fed the diet containing corn oil. Using concentrations of DMN ranging from 12 to 100 mM, microsomes from rats fed the high fat diet activated DMN to produce mutagenesis in S.

Histamine biosynthesis in shock.

The histidine decarboxylase activity of the lung and spleen was determined in rats made resistant to trauma either by prior sublethal exposure or by injection of extracts prepared from the spleens and plasma of trauma-resistant rats. The data describe the posttraumatic period in the normal animal as being associated with an increased histidine decarboxylase activity. In trauma-resistant animals, changes in the enzyme activity were prevented in the lung and were less pronounced in the spleen.