PubMed Health⌕ Search

Biomedical subjects

M Isobe

Publications and source records attributed to M Isobe.

At least 343 records · Page 19Linked to original sources
PubMed1982

A 7-hydroxymethyl sulfate ester as an active metabolite of 7,12-dimethylbenz[alpha]anthracene.

7-Hydroxymethyl-12-methylbenz[alpha]anthracene (7-HMBA), a carcinogenic major metabolite of 7,12-dimethylbenz[alpha]anthracene (DMBA) in liver, was transformed by liver cytosolic sulfotransferase to reactive 7-HMBA sulfate, which is mutagenic toward Salmonella typhimurium strain TA98. The mutagenicity of 7-HMBA in the presence of hepatic sulfotransferase was much higher than that of DMBA or 7-HMBA in the presence of hepatic monooxygenase.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Difference in liver homogenates from Donryu, Fischer, Sprague-Dawley and Wistar strains of rat in the drug-metabolizing enzyme assay and the Salmonella/hepatic S9 activation test.

Comparison studies for detecting differences between liver microsome and S9 preparations from 4 strains (Donryu, Fischer, Sprague-Dawley, Wistar) of young male rats were carried out with pretreatment of the animals by inducers such as PCBs and PB plus 5,6-BF. Each microsome fraction was assayed for the enzymic activity of metabolism of model substrates such as aniline, benzophetamine, BP, DMN and 7-ethoxycoumarin. The hepatic S9 sample was also compared, as regards its metabolizing ability to activate 9 pre-mutagens (2AA, AAF, o-AAT, BP, DAB, DMBA, DMN, m-PDA, quinoline) to directly acting mutagens in the Salmonella/hepatic S9 activation test by using TA98, TA100 and TA1537 strains with or without cytochrome P450 inhibitors (SKF-525A, metyrapone, 7,8-benzo-flavone). In the enzymic assay with PCBs-induced microsomes, BP hydroxylation a strain-specific difference: the microsomes from Fischer and Wistar rats were more effective for metabolizing BP than those from the other strains of rat. The effect of induction by BP plus 5,6-BF for Fischer rats showed relatively higher enzymic activity in the same induction group. Other microsomes prepared from rats with and without induction by PB plus, 5,6-BF did not show a clear-cut strain dependency in the enzymic activities assayed. In the mutation experiments with hepatic S9 samples, the examination of DAB and quinoline revealed a marked strain difference when S9 samples prepared from PCBs-pretreated and PB-plus-5,6-BF-induced rats were used: the S9 sample from Fischer rats was available for activating the two pre-mutagens to directly acting mutagens. No marked difference in the metabolic activation of the remaining 7-pre-mutagens was observed on other S9 preparations. In examinations of mutagenicity activities with the use of three inhibitors, the two S9 preparations made with the two induction methods showed inhibition profiles closely similar to each other. However, there were minor differences in the profiles by these inhibitors. From these findings it was concluded that Fischer rat-liver S9 is useful for detecting mutagens in the metabolic activation test, when induction by PB plus 5,6-BF was used in the Ames Salmonella test.

Animals↗
PubMed1982

Studies on metabolism and toxicity of styrene. IV. 1-Vinylbenzene 3, 4-oxide, a potent mutagen formed as a possible intermediate in the metabolism in vivo of styrene to 4-vinylphenol.

1-Vinylbenzene 3,4-oxide, a putative intermediate in the metabolism of styrene to 4-vinylphenol, was synthesized and examined for its obligatory intermediacy to the phenol, its physical properties, and its mutagenicity toward Salmonella typhimurium TA98 and TA100. The 3,4-oxide had a half-life of 4.3 sec at pH 7.4 in an aqueous solution, and yielded 4-vinylphenol quantitatively without concomitant formation of any trace amount of 3-vinylphenol. The 3,4-oxide had a potent mutagenicity toward the TA100 bacteria but not toward the TA98 strain, whereas it showed a potent cytotoxicity to both of them His+ revertant colonies induced by the 3,4-oxide were 7233/plate at a total dose of 1.0 micromole/plate when it was applied in a sequential manner to the bacterial suspension during the pre-incubation of the testing system. Under the same conditions, benzo[a]pyrene 4,5-oxide and phenyloxirane showed 1283 and 1657 of His+ revertant colonies/plate at 19 nmoles and 10 micromoles/plate, respectively, as the maximal activities. The isomeric arene oxide, 1-vinylbenzene 1,2-oxide, had a longer half-life (1.63 min) than the 3,4-oxide at pH 7.4 in aqueous solution and was specifically rearranged to 2-vinylphenol. The 1,2-oxide also showed more potent mutagenicity to the TA100 strain bacteria than phenyloxirane but weaker than the 3, 4-oxide. 4- and 2-vinylphenols were neither mutagenic nor cytotoxic to the bacteria at concentrations ranging up to 4 micromoles/plate.

Drug Stability↗
PubMed1982

Comparison of mutagenicity and chemical properties of N-methyl-N'alkyl-N-nitrosoureas.

The mutagenic activities of 11 N-methyl-N'-alkyl-N-nitrosoureas were tested on Salmonella typhimurium TA1535 and compared with chemical properties (alkylating activity and decomposition rate). In their relative mutagenicities the N-nitrosoureas that had a cyclic N'-alkyl groups showed far more mutagenic activity than those having a chain N;-alkyl group. M(1-A) NU and M(2-A)NU, which had the most bulky N'-alkyl group in this series, exhibited lethal effects at high concentrations. The mutagenicity showed a small positive correlation with decomposition rates but not with alkylating activities on 4-(p-nitrobenzyl)pyridine. The highest mutagenicity in this series was observed in N-methyl-N'cyclobutyl-N-nitrosourea. These results suggest that, in this series of N-methyl-N'-alkyl-N-nitrosoureas, structural differences in the N'-alkyl groups had great significance in mutagenicity.

Drug Stability↗
PubMed1982

[Effects of beta-blockers and Ca antagonists on diastolic function of the hypertrophied left ventricle: an echocardiographic study].

Left ventricular (LV) relaxation was studied in patients with hypertensive heart disease with LV hypertrophy (HHD, n = 25) and hypertrophic cardiomyopathy (HCM, n = 9), and these data were compared with that of normal controls (n = 20). The effects of oral administration of propranolol (n = 11), pindolol (n = 3), nifedipine (n = 6) and diltiazem (n = 5) in patients with HHD and that of propranolol (n = 9) in patients with HCM were also studied. Isovolumic relaxation time (IRT) was measured using dual M-mode echocardiography and peak normalized rate of change of the LV cavity in early diastole (peak dD/dt/D) was calculated by M-mode echocardiography using a digitizer and microcomputer system. IRT was significantly longer in HHD (112 +/- 24 msec, p less than 0.001) and in HCM (85 +/- 40 msec, p less than 0.05) compared with that of normal subjects (64 +/- 24 msec). The normal value of peak dD/dt/D was 3.8 +/- 0.7 sec-1, and it was significantly lower in HHD (2.7 +/- 0.8 sec-1, p less than 0.001). It was also lower in HCM (3.2 +/- 0.8 sec-1), but without a statistical significance. In HHD there was a significant relationship (r = -0.611, p less than 0.01) between peak dD/dt/D and wall thickness of the LV (interventricular septum + LV posterior wall). There was no significant change in IRT before and after the administration of beta-blockers and calcium antagonists except nifedipine in HHD (before: 116 +/- 28 msec, after: 80 +/- 14 msec, p less than 0.005). It was probably due to the effect of an accompanied decrease in heart rate. However, peak dD/dt/D was significantly increased in both HHD and HCM groups after the administration of propranolol, pindolol, nifedipine and diltiazem. These data show that LV relaxation is abnormal in the hypertrophied LV. Although the genesis of this abnormality is not clear, there seems to be a close relationship between the relaxation abnormality and increased LV mass in HHD. Oral administration of propranolol, pindolol and diltiazem for patients with HHD and propranolol for patients with HCM seems to improve the abnormal LV relaxation of each disease.

Adrenergic beta-Antagonists↗
PubMed1982

[Effects of administration of an antineoplastic agent into the bronchial artery].

Morphological observation was performed to see the effect of bronchial arterial infusion therapy (BAI) of mitomycin C (MMC) and also of the ischemia to the transplanted bronchial carcinoma. Single shot of 2mg/kg of MMC showed destructive changes on the tumor. Single shot of 3mg/kg and repeated administration of MMC brought relatively severe intra-arterial inflammatory changes such as intimal edema, thickening and proliferation which suggested ischemic effect on the tumor due to poor perfusion from stenosis or obstruction of the vessels. On the other hand a simple ligation of the artery also brought about more than moderate destructive changes in the tumor. Therefore, mechanisms of the effect of the BAI of MMC to the lung tumor might involve the secondary effect from ischemia in addition to the effect of MMC itself.

Animals↗
PubMed1980

Cholesterol alpha- and beta-epoxides as obligatory intermediates in the hepatic microsomal metabolism of cholesterol to cholestanetriol.

A high performance liquid chromatographic method for the good separation and direct determination of cholesterol alpha-epoxide (5,6 alpha-epoxy-5 alpha-cholestan-3 beta-ol) and beta-epoxide (5,6 beta-epoxy-5 beta-cholestan-3 beta-ol) was introduced to the study of microsomal lipid peroxidation-mediated oxygenation of the cholesterol double bond. In the presence of NADPH, FeSO4, and ADP, bovine liver microsomes converted [4-14C] cholesterol to the alpha-epoxide, beta-epoxide, and cholestanetriol (5 alpha-cholestane-3 beta,5,6 beta-triol) in the ratio 1.0:4.3:0.7. Obligatory intermidiacy of both cholesterol alpha- and beta-epoxides and essential role of microsomal cholesterol epoxide hydratease in the conversion of cholesterol to cholestanetriol were established by using the isotope trapping method as well as the cholesterol epoxide hydratase inhibitor, 5,6 alpha-imino-5 alpha-cholestan-3 beta-ol. Hepatic microsomal P-450 played no appreciable role in the epoxidation of cholesterol. Microsomal cholesterol epoxide hydratase was with no doubt found to differ in nature from microsomal xenobiotic epoxide hydratase. Microsomal hydrolysis of styrene oxide and safrole oxide (0.1 mM each) was almost completely inhibited by 3,3,3-trichloro-1-propene oxide (1 mM) but not by 5,6 alpha-imino-5 alpha-cholestan-3 beta-ol (1 mM). However, microsomal hydrolysis of both cholesterol alpha- and beta-epoxides was remarkably accelerated by 3,3,3-trichloro-1-propene oxide and inhibited by 5,6 alpha-imino-5 alpha-cholestan-3 beta-ol.

Animals↗