Inhibition by selenium of intrahepatic cholangiocarcinoma induction in Syrian golden hamsters by N'-nitrosobis(2-oxopropyl)amine.

The effects of selenium supplementation on induction of cholangiocarcinomas and related precancerous lesions in female Syrian Golden hamsters by N'-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Four-week-old animals were divided into two groups according to the selenium level contained in the drinking water (0.1 ppm or 4.0 ppm) and fed a purified diet containing less than 0.05 ppm of the trace element. Starting at Week 4 of the experiment, hamsters were administered 10 weekly injections of BOP (10 mg/kg body wt) and then killed 18 weeks after the last carcinogen administration. Animals receiving physiological saline alone served as controls. Cholangiocellular carcinomas tended to be reduced, and putative preneoplastic lesions of cholangiofibrosis were significantly decreased in the high-as opposed to the low-selenium groups in terms of both incidence rate and number per effective animal. The respective high and low selenium values for incidence and number were 24/38% and 0.34/0.66, respectively, for cholangiocarcinomas and 50/89% and 1.21/8.44, respectively, for cholangiofibroses. Proliferation of intrahepatic bile ducts was also significantly inhibited in the high-selenium group along with cyst formation. Biochemical investigation revealed both selenium level and glutathione peroxidase activity to be significantly greater in the high-than in the low-selenium group livers. The results thus suggest that selenium may inhibit BOP-induction of bile duct lesions, possibly via glutathione peroxidase-mediated alteration of carcinogenesis.

Inhibitory effect of selenium on hamster pancreatic cancer induction by N'-nitrosobis(2-oxopropyl)amine.

The effect of selenium intake on the development of pancreatic cancer was investigated in female Syrian golden hamsters. Four-week-old hamsters were divided into 2 groups according to the selenium level in their drinking water and were fed a purified diet containing less than 0.05 ppm selenium. Starting 4 weeks later, groups received 10 s.c. injections at weekly intervals of N'-nitrosobis(2-oxopropyl)amine (BOP) dissolved in saline, while controls received saline alone. When the animals were killed 18 weeks after the last injection, palpable tumors were less frequent in the high-selenium group than in animals receiving low-selenium supplement, the numbers of histologically diagnosed cancerous lesions also being significantly reduced by high selenium intake. The selenium level and glutathione peroxidase activity in serum and pancreas were significantly greater in the high-selenium group. Moreover, selenium levels and glutathione peroxidase activity were both significantly higher in tumor-bearing tissue. The results suggest that glutathione peroxidase is involved as an intermediate factor in prevention of carcinogenesis by selenium.

Branched-chain amino acid-supplemented nutritional support after gastrectomy for gastric cancer with special reference to plasma amino acid profiles.

Preoperative plasma aminograms constructed for 63 patients expected to undergo gastrectomy for gastric cancer at different stages showed markedly lower concentrations of many plasma amino acids in the Stage IV and recurrent cases. The amino acid levels were inversely proportional to tumor size. On the other hand, preoperative arteriovenous differences in free amino acid levels were positive in Stage I cancer but negative in Stage IV cancer, indicating that intake of amino acids by the skeletal muscles exceeded the outflow in Stage I, whereas there was a net loss of amino acids from the skeletal muscles in advanced cancer. The amount of amino acids actually lost from the skeletal muscles after muscular loading in Stage I cancer also surpassed that in Stage IV cancer. Administration of TPN solution supplemented with 31% branched-chain amino acids (BCAA) might favorably influence muscle protein metabolism in gastric cancer patients by inhibiting protein degradation and promoting synthesis, as treatment was more effective than 21% BCAA-enriched TPN.