pCNBによるメト・ヘモグロビン形成機構に関する研究 : 第3報 pCNBの各中間代謝物のメト・ヘモグロビン形成機構について

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1. Met-hemoglobin formation with the aminoderivative (p-chloraniline). As reported in Reports 1 and 2, amino-derivative of pCNB showed remarkable met-hemoglobin. When liver homogenate or slices were added in the system consisted of incubation medinm, p-CL-aniline and human blood, remarkable formation was observed as shown in Figure 1. According to this result, I think that the amino derivate itself cannot form the met-hemoglobin, but that it can be a met-former through being metabolized by liver cells to an active metabolite. In this case, it is easily considered that, turned into aminophenol. the amino-derivate forms met-hemoglobin but that the conjugating aminophenol derivate (5-Cl-2-aminophenol) can form only an amount of a half or one fifth or less of the met-hemoglobin as compared with the case of amino (as shown by the in vivo experiment, cf. Fig. 3 of Report 1), so the met-hemoglobin formation with the amino-detivate could not be considered to be performed only by way of its aminophenol. 2. Mechanisms of each metabolite. Summarized results of the experiments till now are showed in the Table 1. According to the results, the mechanisms of each metabolite were considered as follows: 1) The nitroso-derivate (p-Cl-nitrosobenzene) has a function of direct oxidation of hem-Fe, 2) the hydroxylamino-derivate (p-Cl-phenylhydroxylamine) may act as a perturbator to globin-protein and it or its oxydized compound oxydized hem-Fe, 3) the amino-derivate, obviously, is converted into an active substance by liver or other organs, and affects hemoglobin, and 4) the aminophenol affects as a perturbator to globin, and its oxidized compound (iminoquinone) oxidizes hem-Fe. 3. Specific inhibition of aminophenol-derivative on aerobic glycolysis. Formerly, Onishi, a member of our laboratory, investigating the influences of various derivatives of anthranilic acid manometrically on respiration and glycolysis of Ehrlich ascites tumor cells, observed that the anthranilic acid and its aminophenol-derivatives (ortho and para) remarkably inhibited only aerobic glycosis of the tumor cells specifically at low concentrations in which respiration and anaerobic glycolysis were not inhibited (10^<-4> or 10^<-5> mol). I, with collaboration of Fukui and Takatsuka, examining the inhibition by these derivatives and by 2-carboxy, 5-aminophenol by means of chemical estimation of lactate, noticed the same results. So supposing that the action observed was caused by the aminophenol structure of these compounds, I also tested p-aminophenol, a simple and typical aminophenolic compound. Results showed specific inhibition in aerobic glycolysis at low concentrations in which oxygen-uptake and anaerobic lactate-formation were not inhibited (cf. Table 2). The action of specific inhibition on lactate-formation is probably caused by a decrease of NAPH (reduced form) that results from over-oxidation of NAPH cattalyzing the lactate-formation, or inhibition on reduction of NAP (oxidized form), by oxidized aminophenol. Since the inhibiting does not occur at anaerobic conditions, it is presumed that compounds of amino or aminophenol oxidize NAPH in aerobic conditions by their oxidized forms and deprived of its activity. Reduction of met-hemoglobin to hemoglobin is catalyzed by NAPH, so decrease of NAPH by amino or aminophenol may probably be one of the mechanisms of met-hemoglobin formation.
社団法人日本産業衛生学会の論文
1968-09-20

pCNBによるメト・ヘモグロビン形成機構に関する研究 : 第3報 pCNBの各中間代謝物のメト・ヘモグロビン形成機構について

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