Biomedical subjects

H K Watanabe

Publications and source records attributed to H K Watanabe.

27 records · Page 2Linked to original sources

PubMed1984

Effects of steroid hormones and xenobiotics on the pubertal development of UDP-glucuronosyltransferase activities towards androsterone and 4-nitrophenol in Wistar rats.

Oestradiol benzoate, testosterone propionate, progesterone, corticosterone, 3-methylcholanthrene and phenobarbital were administered to Wistar rats at the pubertal period, and their effects on hepatic UDP-glucuronosyltransferase activities were determined. Pretreatment with oestradiol benzoate had a temporary suppressive effect on androsterone UDP-glucuronosyltransferase activity in rats with the high-activity phenotype of androsterone glucuronidation. The effect was marked in 40-day-old rats, but was not found in older rats. Androsterone UDP-glucuronosyltransferase activity was induced by phenobarbital in rats with the high-activity phenotype, but not in rats with the low-activity phenotype. Foster-feeding experiments showed that breast milk did not alter the genetically determined expression of androsterone UDP-glucuronosyltransferase activity in Wistar rats. In contrast, 4-nitrophenol UDP-glucuronosyltransferase activity was not affected by steroid hormones, but was highly induced by 3-methylcholanthrene.

Androsterone↗

PubMed1984

Rat liver sulfotransferases: effects of gonadal hormones and other factors on enzyme activities.

Estradiol benzoate (EB), testosterone propionate (TP), progesterone (PG), corticosterone (CS), 3-methylcholanthrene (MC) and phenobarbital (PB) were administered to Wistar rats and their effects on hepatic sulfotransferase (ST) activities toward androsterone (AD) and 4-nitrophenol (NP) were determined. ST activity toward AD was increased by pretreatment with EB and PG in male rats. ST activity toward NP was increased by administration of TP and PG in females, whereas the enzyme activity was suppressed by pretreatment with EB in males. Administration of CS, MC and PB did not significantly affect ST activities toward AD and NP. These results indicate that sex difference in rat liver ST activities appears to be primarily regulated by androgenic, estrogenic and progestational hormones.

Aging↗

PubMed1984

Recognition and treatment of acute alcohol withdrawal syndromes.

The alcohol withdrawal syndromes are generally self-limited processes from which spontaneous recovery can be anticipated. To achieve this outcome, the various types of withdrawal must be managed in such a way as to prevent the occurrence of life-threatening situations. This begins with a good initial evaluation, followed by the appropriate pharmacologic and behavioral steps to control the severity of withdrawal symptoms and to manage complications. Once the withdrawal process is completed, the patient can then be entered into a long-term treatment program.

Acute Disease↗

PubMed1982

Developmental alteration of hepatic UDP-glucuronosyltransferase and sulphotransferase towards androsterone and 4-nitrophenol in Wistar rats.

Postnatal development of hepatic UDP-glucuronosyltransferase and sulphotransferase activities towards androsterone and 4-nitrophenol as well as cytochrome P-450 contents was studied in male and female Wistar rats. The rats with high and low UDP-glucuronosyltransferase activity towards androsterone were classified by the genotype of the parent animals. UDP-glucuronosyltransferase activity towards androsterone began rapidly to enhance after 30 days of age in the high-activity group, whereas the transferase activity remained low throughout in the low-activity group. Such a striking difference was not observed in UDP-glucuronosyltransferase activity towards 4-nitrophenol, sulphotransferase activity towards androsterone and 4-nitrophenol, and cytochrome P-450 contents. Sex-based difference in the sulphotransferase activity was marked after 30 days of age. Sulphotransferase activity towards androsterone was much higher in adult females than in adult males, whereas higher sulphation activity towards 4-nitrophenol was found in adult males. The results also indicate that the low level of the UDP-glucuronosyltransferase activity did not lead to compensatory stimulation of the sulphotransferase activity.

Age Factors↗

PubMed1982

Classification and genetic expression of Wistar rats with high and low hepatic microsomal UDP-glucuronosyltransferase activity towards androsterone.

Male and female Wistar rats with high and low hepatic microsomal UDP-glucuronosyltransferase activity towards androsterone were classified by partial hepatectomy. The breeding experiments between the classified high-activity and low-activity rats show that the genetic expression of the high transferase activity is inherited in an autosomal dominant fashion.

Androsterone↗

PubMed1982

Carcinogenicities of 3-methoxy-4-aminoazobenzene, N-hydroxy-3-methoxy-4-aminoazobenzene and related azo dyes in the mouse.

The carcinogenicities of 2-methoxy-4-aminoazobenzene and 3-methoxy-4-aminoazobenzene (2-MeO-AAB and 3-MeO-AAB) and their N-hydroxy derivatives (N-OH-2-MeO-AAB and N-OH-3-MeO-AAB) were tested in (C3H X C57BL/6) F1 mice. Topical sc injections, twice weekly for 8 weeks, of 4 or 8 mumol of N-OH-3-MeO-AAB dissolved in 0.1 ml of olive oil containing 10% dimethyl sulfoxide induced fibrosarcomas at the site of application. Similar treatment with 3-MeO-AAB or 2-MeO-AAB as well as N-OH-2-MeO-AAB failed to induce sarcomas. Oral administration of 0.09% 3-MeO-AAB in the diet for 13 months induced hepatic tumors in female mice but not in males. 2-MeO-AAB did not induce tumors in male or female mice. The relationship between carcinogenicity, mutagenicity, the ability to induce unscheduled DNA synthesis, and the metabolism of these azo dyes is discussed.

Animals↗

PubMed1981

Amino acid conjugation of N-hydroxy-4-aminoazobenzene dyes: a possible activation process of carcinogenic 4-aminoazobenzene dyes to the ultimate mutagenic or carcinogenic metabolites.

The activation process of N-hydroxy-4-aminoazobenzene (N-OH-AAB) dyes, proximate mutagenic or carcinogenic metabolites of AAB dyes, to the ultimate mutagenic or carcinogenic metabolites was studied by the use of an amino acid conjugation (aminoacylation) system catalyzed by yeast seryl-tRNA synthetase and [3H]ATP. A potent mutagen, N-hydroxy-3-methoxy-AAB (N-OH-3-MeO-AAB), as well as a non-mutagen, N-OH-2-MeO-AAB, were equally susceptible to N-O-serine conjugation. A weak mutagen, N-OH-AAB, and a moderate mutagen, N-OH-2,5-diMeO-AAB, were also susceptible to the aminoacylation, but to a lesser extent than the 2- or 3-methoxyl homologs. In contrast, N-hydroxy-N-methyl-4-aminoazobenzene and a moderate mutagen, N-OH-4'-MeO-AAB, were not susceptible to the aminoacylation. The ability of these N-OH-AAB dyes to bind with nucleic acid after serine conjugation was proportional to the susceptibility of the dyes to serine conjugation. Serine conjugates of N-OH-AAB dyes reacted with poly G, but not with poly A, poly C or poly U, suggesting that the azo dyes selectively bind with guanine base of nucleic acids. The susceptibility of N-OH-AAB dyes to aminoacylation was compared with the carcinogenic, mutagenic and unscheduled DNA synthesis-inducing activities of these and the mother AAB dyes.

Animals↗

PubMed1981

Mutagenicity of 4-aminoazobenzene, N-hydroxy-4-aminoazobenzene, 4-nitrosoazobenzene, 4-nitroazobenzene, and their ring methoxylated derivatives on Salmonella.

The mutagenicities of 4-aminoazobenzene (AAB), N-hydroxy-4-aminoazobenzene, 4-nitroazobenzene, and their 2-, 3-, 4'-methoxyl and 2,5-dimethoxyl derivatives, and 2- and 3-methoxy-4-nitrosoazobenzene were examined on Salmonella typhimurium TA98 and TA100. The activities of AAB dyes upon S-9 metabolic activation were related to their carcinogenic activities in the rat. The potent carcinogen 3-methoxy-AAB was a potent mutagen for both tester strains. The moderate or weak carcinogens 4'-methoxy-AAB and AAb were moderate or weak mutagens for one or both of the tester strains. The non-carcinogens 2-methoxy-AAB and 2,5-dimethoxy-AAB were non-mutagenic. In contrast to AAB dyes, N-hydroxy-AAB dyes showed greater mutagenicity than the mother AAB dyes, without S-9 treatment. 4-Nitroazobenzene dyes and 4-nitrosoazobenzene dyes showed mutagenicity without S-9 treatment, and the activities were related to those of the corresponding N-hydroxy-AAB dyes. All 4-nitroazobenzene dyes were mutagenic in the presence of S-9, suggesting the production of mutagens other than N-hydroxy-AAB dyes by the S-9 treatment. The cytotoxicity of azo dyes to bacteria had no apparent relation to the mutagenic activity of the azo dyes. Incubation of 4-nitroazobenzene dyes with TA100 bacteria yielded N-hydroxy-AAB dyes. The synthesis and properties of new N-hydroxy-AAB dyes, 4-nitroazobenzene dyes and 4-nitrosoazobenzene dyes are described.

Azo Compounds↗

PubMed1981

Unscheduled DNA synthesis induced by 4-aminoazobenzene, N-hydroxy-4-aminoazobenzene, and their derivatives in primary cultures of rat and mouse hepatocytes.

The ability of carcinogenic and non-carcinogenic aminoazo dyes to induce unscheduled DNA synthesis (UDS) in primary cultures of hepatocytes of 3 strains of rats and 2 strains of mice was examined by means of microautoradiography. Azo dyes tested were 4-aminoazobenzene (AAB) and 4 of its ring methoxyl (MeO) derivatives, their N-hydroxy (N-OH) derivatives, N-methyl-4-aminoazobenzene (MAB) and its N-bezoyloxy derivative, and N,N-dimethyl-4-aminoazobenzene (DAB). All carcinogenic aminoazo dyes (AAB, 3-MeO-AAB, 4'-MeO-AAB, MAB and DAB), but not the non-carcinogenic dyes (2-MeO-AAB and 2,5-diMeO-AAB), induced UDS in rat hepatocytes as well as mouse hepatocytes. N-Hydroxy derivatives of AAB and its 3- and 4'-MeO derivatives elicited higher levels of UDS than did the corresponding mother aminoazo dyes. N-OH-2-MeO-AAB was as inactive with rat hepatocytes as the mother dye. N-OH-2,5-diMeO-AAB, however, elicited a definite level of UDS, in contrast to the mother 2,5-diMeO-AAB. N-Benzoyloxy-MAB, a prototype compound of the ultimate carcinogenic metabolite of MAB, was as active as the mother MAB. N,-OH-3-MeO-AAB induced UDS more rapidly than did 3-MeO-AAB. The UDS elicited by 3-MeO-AAB was found to end within a few hours after releasing the hepatocytes from the azo dye.

Animals↗