Recently, we have isolated a new collagenous molecule from chicken hyaline cartilage after limited pepsin digestion. This molecule, which contains interchain disulfide bonds, has been called the high molecular weight fraction or HMW [Reese, C. A., & Mayne, R. (1981) Biochemistry 20, 5443-5448]. We now present a detailed model for the structure of HMW, the model being derived from analyses both of components of HMW obtained after denaturation either with or without reduction and from electron microscopic observation of replicas of HMW obtained after rotary shadowing. We propose that HMW is a typical, triple-helical collagen molecule of length 134 nm, in which one of the chains has been cleaved at a distance of 96 nm from one end of the triple helix, while the other two chains remain uncleaved. The result of this cleavage is the appearance of a recognizable kink in molecules of HMW when visualized after rotary shadowing.
Female inbred C3H/St mice infected with the Bittner Milk Particle, develop mammary adenocarcinoma with 27% incidence if maintained on a Torula Yeast diet supplemented with 1 ppm of selenium (organically bound, in yeast). Animals switched from the 1 ppm Se diet to a diet containing only 0.15 ppm Se after reaching the age of 13.8 months develop mammary tumors rapidly during their remaining lifespan, the overall tumor incidence reaches 69%, not statistically different from the 77% incidence of tumors observed in animals maintained on the 0.15 ppm Se diet over their entire post-weaning life span. Conversely, animals changed from the 0.15 ppm Se diet to that containing 1.0 ppm Se at the age of 13.8 months develop mammary tumors with a total incidence of only 46%, significantly lower (P < 0.05) than in the 0.15 ppm Se control group. This study demonstrates that dietary selenium prevents and retards tumor development only as long as it is supplied in adequate amounts, consistent with its role as a non-accumulative trace nutrient.
Selenium added to the diet significantly lowers the incidence of spontaneous mammary adenocarcinoma in female inbred C3H/St mice infected with the Bittner Milk Factor. Lead, 5 ppm, added to the drinking water in the form of the acetate, diminishes the uptake of selenium and reduces its anticarcinogenic effects, causing mammary tumors to appear with the same high incidence as in Se-unsupplemented controls. At higher lead concentrations in the drinking water (25 ppm), the overall tumor incidence is lowered, but tumor growth is significantly accelerated and the survival of tumor-bearing mice is shortened. Under the conditions of administration chosen, lead acts as a selenium antagonist and lowers the concentrations of selenium in liver, kidney, and spleen. The deposition of selenium, copper, and arsenic in bone is increased as compared to lead-unexposed controls.
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