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-Canola and some other types of oil unusually shorten the survival of stroke-prone spontaneously hypertensive rats (SHRSP), compared with soybean oil, perilla oil and animal fats. Since differential effects of canola and soybean oil on steroid hormone metabolism were suggested by a preliminary DNA microarray analysis as a reason for this, the steroid hormone levels in the serum and tissues of SHR-SP fed different oils were investigated. The testosterone levels in the serum and the testes were found to be significantly lower in the canola oil group than in the soybean oil group, while no significant differences were detected in the corticosterone and estradiol levels in tissues. In a second experiment, it was found that hydrogenated soybean oil, with a survival-shortening activity comparable to that of canola oil, also decreased the testosterone level in testes to a similar degree. The testosterone-lowering activity of canola and hydrogenated soybean oil observed in SHRSP was considered in relation to other factors possibly affecting the physiology of SHRSP.

Senescence-accelerated mouse-prone (SAMP1; SAMP1@Umz) is an animal model of senile amyloidosis with apolipoprotein A-II (apoA-II) amyloid fibril (AApoAII) deposits. This study was undertaken to investigate the effects of dietary fats on AApoAII deposits in SAMP1 mice when purified diets containing 4% fat as butter, safflower oil, or fish oil were fed to male mice for 26 weeks. The serum HDL cholesterol was significantly lower ( P Ͻ 0.01) in mice on the diet containing fish oil (7.4 ؎ 3.0 mg/dl) than in mice on the butter diet (38.7 ؎ 12.5 mg/dl), which in turn had significantly lower ( P Ͻ 0.01) HDL levels than mice on the safflower oil diet (51.9 ؎ 5.6 mg/dl). ApoA-II was also significantly lower ( P Ͻ 0.01) in mice on the fish oil diet (7.6 ؎ 2.7 mg/dl) than on the butter (26.9 ؎ 7.3 mg/dl) or safflower oil (21.6 ؎ 3.7 mg/dl) diets. The mice fed fish oil had a significantly greater ratio ( P Ͻ 0.01) of apoA-I to apoA-II, and a smaller HDL particle size than those fed butter and safflower oil. Severe AApoAII deposits in the spleen, heart, skin, liver, and stomach were shown in the fish oil group compared with those in the butter and safflower oil groups (fish oil Ͼ butter Ͼ safflower oil group, P Ͻ 0.05). These findings suggest that dietary fats differ in their effects on serum lipoprotein metabolism, and that dietary lipids may modulate amyloid deposition in SAMP1 mice.

To elucidate the mechanism underlying suppression by curcumin of esophageal carcinogenesis induced by NMBA, we evaluated the CYP level and mutagenic activation of environmental carcinogens, by immunoblot analyses and Ames preincubation test, respectively, and bilirubin, 4-nitrophenol and testosterone UDPGT activities in F344 rats treated with curcumin and/or NMBA. No significant alterations in the hepatic levels of constitutive CYP proteins, mutagenic activation by liver S9 or hepatic UDPGT activities were produced by subcutaneous treatment with 0.5 mg/kg NMBA for 5 weeks and/or feeding of 0.05% and 0.2% curcumin for 6 weeks. In contrast, gavage of 0.2% curcumin decreased esophageal CYP2B1 and 2E1 by up to 60%, compared with vehicle control. Similarly, intragastric treatment with 270 mg/kg curcumin decreased esophageal and gastric CYP2B1 and CYP2E1, but not in lung, kidney or intestine. Conversely, large intestinal CYP2B1 was 2.8-fold higher in the treated rats than in control rats. Mutagenic activities of NOC, including NMBA, in the presence of esophagus and stomach S9 were markedly decreased in the treated rats, whereas those in the presence of large intestine S9 were 2.2-3.0-fold above control. These results show that modifying effects of curcumin on esophageal carcinogenesis can be attributed to a decrease in metabolic activation of NMBA by esophageal CYP2B1 during the initiation phase, without the contribution of metabolic activation and inactivation by liver. Further, the present findings suggest the potential of curcumin for modification of gastric and intestinal carcinogenesis initiated with NOC. (Cancer Sci 2006; 97: 896-904) H uman esophageal cancer has been closely associated with exposure to nitrate and nitrite, which are precursors of NOC, and exposure to NMBA is also associated with an increased risk of human cancer in the esophagus in China. (1)(2)(3)(4) In fact, NMBA is known to be the most potent carcinogen for rat esophagus, irrespective of its mode of administration. (5,6 ) It has been shown that esophageal mucosa microsomes from male Sprague-Dawley rats can form benzaldehyde and formaldehyde from NMBA at rates 1/5 and 1/60 of hepatic levels of both metabolites, respectively, and the metabolisms are inhibited more than 95% by CO and 70% by SKF525A, typical CYP inhibitors.(7) O 6 -methylated guanine level in rats given NMBA is six times higher in esophagus DNA than in liver DNA, (8) and isothiocyanates markedly decrease the incidence and multiplicity of NMBA-induced esophageal tumors, with inhibition of esophageal DNA methylation in F344 rats.(9) Further, it has been shown that ethanol has an enhancing effect on DEN-induced esophageal tumorigenesis in F344 rats, (10) with enhancement of metabolic activation of DEN by hepatic CYP2E1.(11) These findings indicate the importance of metabolic activation of NMBA by the target organ and/or liver during the initiation phase, and some NOC are known to be metabolized in the esophagus at a relatively high rate, often leading to high levels of esophageal D...