Inhibition of carcinogenesis: Vitamin C and the prevention of gastric cancer.
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Biomedical subjects
Publications and source records attributed to H F Mower.
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Following migration to Hawaii, the Japanese have acquired the same risk of developing large bowel cancer as that experienced by Caucasians. This tumor is uncommon in Japan. Other conditions are also more common in Hawaii Japanese, e.g., myocardial infarction, severe atherosclerosis, diverticulosis, and polyposis of the colon. Comparative studies in Hawaii and Japan suggest that the basis of these differences is probably related to the consumption of characteristically western foods by Hawaii Japanese.
Some workers have associated fecal bile acids with colon cancer frequency. They suggest that the risk for colon cancer increases with a rise in the level of total and degraded fecal bile acids. The Japanese in Hawaii, who are at high risk for this cancer, had higher concentrations of deoxycholic acid (a degraded bile acid) in their fecal specimens than did the people in Akita, Japan, who are at low risk. However, the findings for the other bile acids were unremarkable or inconsistent. These data were suggestive, but not strongly supportive, of a relationship between fecal bile acid patterns and colon cancer risk.
Fecal samples of 165 Japanese men in Hawaii, age 43 to 74, were analyzed for bile acid content by their conversion to the methyl ester and the trimethylsilyl ether derivative followed by separation on a gas chromatograph. The arithmetic mean of total bile acids for the 165 specimens was 10.96 mg/g dry weight feces. Each of the following bile acids was detectable in over 77% of the fecal specimens: cholic, deoxycholic, lithocholic, and cholanic acid. The intake of Western foods was not positively correlated with the fecal content of secondary or modified bile acids, even though other workers have observed that these bile acids predominated in persons from Westernized countries. Two of the Japanese foods were negatively correlated with the levels of modified bile acids, which suggested that these foods contributed to a decrease in modified bile acids in fecal specimens. Fecal bile acid measurements appeared to be associated with age, but not with weight, height, or serum cholesterol levels.
A series of rec-Escherichia coli strains were tested for their sensitivity to four known carcinogenic compounds by examination of a zone of inhibited bacterial growth around a central well containing the test chemical. The mutants recA-, recB-, recC-, and recA- recB- recC- were all more sensitive to the mutagens than the parental strain AB1157. The recB- recC- strain was examined with a larger series of compounds and was found to respond to many of the substances in a similar way as the Salmonella typhimurium strains of Ames but with some notable exceptions. Nitrosamines, with rat liver microsomal activation, could be detected at lower levels and a group of aromatic amino compounds failed to react with these rec-E. coli. An unusual feature of these rec-mutants is their sensitivity to mixtures of nitrosamines and 2-acetyl amino-fluorene in the absence of microsomal activation.
The primary aim of the Japan--Hawaii Cancer Study was to identify factors that could explain the changes in cancer risk experienced by Japanese who migrated to Hawaii. Many investigations were conducted in this long-term prospective study since its inception in 1971. Among the findings that relate to gastrointestinal carcinoma were the following: 1) Bowel transit time does not appear to be related to the occurrence of large bowel cancer or to any of the benign conditions with which it is associated; 2) adenomatous and hyperplastic polyps, as well as diverticula, are much more prevalent among autopsy specimens from Japanese who had lived in Hawaii than of those in Japan; 3) adenomatous polyps and diverticula are positively associated with atherosclerosis in the necropsy population in Hawaii; 4) although the incidence of the diffuse histopathologic type of gastric cancer does not differ appreciably among the Japanese in Hawaii and Japan, the migrants have a significantly lower incidence of the intestinal type of stomach cancer; and 5) case-control studies indicated that the two conditions frequently associated with gastric carcinoma, i.e., gastric ulcer and intestinal metaplasia of the stomach, are associated with high salt intakes and adherence to the traditional Japanese diet.
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Ackrell, B. A. C. (University of Hawaii, Honolulu), R. N. Asato, and H. F. Mower. Multiple forms of bacterial hydrogenases. J. Bacteriol. 92:828-838. 1966.-Extracts of certain bacterial species have been shown by disc electrophoresis on polyacrylamide gel to contain multiple hydrogenase systems. The hydrogenase enzymes comprising these systems have different electrophoretic mobilities and produce a band pattern that is unique for each bacterial species. Of 20 bacterial species known to possess hydrogenase activity and which were examined by this technique, only the activities of Clostridium tetanomorphum and C. thermosaccharolyticum could be attributed, at pH 8.3, to a single hydrogenase enzyme. This multiplicity of hydrogenase forms was found both in bacteria which contain mostly soluble hydrogenases and in those where the hydrogenase is predominantly associated with particulate material. When solubilization of this particulate material could be effected, at least two solubilized hydrogenases were released, and, of these, one would have the same electrophoretic properties (i.e., R(F)) as one of the soluble hydrogenases already present in small amounts within the cell. Different growth conditions for various types of bacteria, such as the nitrogen source, the degree of aeration, and photosynthetic versus aerobic growth in the dark, as well as the conditions under which the cells were stored, markedly affected the hydrogenase activity of the cells, but not their hydrogenase band pattern. The disc electrophoresis technique proved to be 10 times more sensitive than the manometric technique in detecting hydrogenase activity.
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Carbofuran (CF), an insecticide and nematocide, is metabolically oxidized to two less toxic forms, 3-hydroxycarbofuran and 3-ketocarbofuran. The N-nitroso derivatives of carbofuran and its metabolites were synthesized by reaction with nitrite under acidic conditions. Products of the reaction were obtained by extraction, identified by thin-layer chromatography, and purified by silica gel column chromatography. All three nitroso derivatives reacted positively with Gries reagent and gave characteristic triplet absorption spectra (387, 402, and 422 nm). Structural confirmation was by nuclear magnetic resonance and mass spectroscopy. Mutagenicity was determined by the Ames assay method with Salmonella typhimurium strains TA98 and TA100. The nitroso derivatives of all three compounds responded similarly, given a mutation ratio of 45 at 5 micrograms per plate on TA100. In addition, all three produced chromosome aberrations in Chinese hamster ovary (CHO) cells. Only two of the three (nitrosocarbofuran and 3-hydroxynitrosocarbofuran) were also capable of inducing large numbers of sister chromatid exchanges in the same cells. Observed variations in maximum mutagenicity in the Ames test and the ability to induce sister chromatid exchanges in CHO cells are consistent with the stability of the compounds in aqueous solution.
A novel lipophilic yellow pigment has been isolated from human and primate tissue. Field-desorption mass spectrometry suggests a molecular ion of mass 645-700, and electron-impact mass spectrometry gives a major fragment ion at 603.5348, which is consistent with the elemental composition C37H69N3O3. The ultraviolet/visible spectrum has two major absorption peaks at 423.6 nm and 398.8 nm and a smaller peak at 377.8 nm. The adrenal gland contains the highest concentration of the pigment; it is also present in the colon, kidney, lung, spleen, and stomach tissue. It is not present in brain or liver. The pigment has not been detected in the rat, mouse, cow, pig, or dog.