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T Kawachi

Publications and source records attributed to T Kawachi.

At least 37 records · Page 2Linked to original sources
PubMed1983

Classification of compounds by cluster analysis of Ames test data.

The dose-response curves for various compounds in the Ames test were analyzed by combining the least-squares method with cluster analysis. The following theoretical equation was employed: m(x) = (B + Sx)exp(-Tx), where m(x) is the number of revertants at the dose of x; B, the background number; S, the mutagenicity rate; and T, the toxicity rate. This equation is derived from a one-hit model modified to take account of the toxicity, and the parameters B, S and T are determined by applying the least-squares method for the fitting between theoretical and experimental dose-response curves with the use of the program package SALS (statistical analysis with least-squares fitting). With the values for B, S and T thus obtained, cluster analysis can clearly separate mutagenic and non-mutagenic compounds. Moreover, when cluster analysis into six groups is carried out, each group has quite characteristic parameter values. Consequently, this procedure is very useful for the classification of compounds according to the nature of the dose-response curve, that is, according to the nature of their mutagenic activity.

Carcinogens↗
PubMed1983

Genetic control of susceptibility of rats to gastric carcinoma.

Genetic control of the induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in susceptible ACI rats, resistant Buffalo rats, and their F1 and F2 offspring. Both sexes of all strains, initially 7 to 9 weeks old, were given MNNG at a concentration of 83 micrograms/ml in their drinking water for 32 weeks and were sacrificed at experimental Week 72. The incidence of gastric adenocarcinoma in ACI rats was 80% in males and 47% in females; in Buffalo rats, the incidence was 18% in males and 0% in females. F1 hybrids showed the same resistance to MNNG as did Buffalo rats; the incidence of gastric adenocarcinoma was 17% in males and 8% in females. These results suggest that resistance to induction of gastric adenocarcinoma by MNNG is a dominant characteristic. The incidence of gastric adenocarcinoma in the F2 generation was 36% in males and 14% in females, which is close to the 3:1 ratio expected from the segregation of a single resistant gene. In ACI and Buffalo strains and their hybrids, males were more susceptible than females to induction of gastric carcinoma by MNNG. Intestinal tumors were observed mainly in the duodenum and jejunum in both strains and their hybrids, and the incidences were as follows: ACI: males, 67% and females 42%; Buffalo: males, 12% and females, 18%; F1: males, 18% and females, 15%; and F2: males, 15% and females, 19%. Thus, there seems to be a common genetic basis for both gastric and intestinal carcinogenesis by MNNG.

Animals↗
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

Carcinogenicity in rats of the mutagenic compounds 1-nitropyrene and 3-nitrofluoranthene.

1-Nitropyrene and 3-nitrofluoranthene are present in diesel exhaust, in pollutants in air, and were also present in certain xerographic toners and copies. Their carcinogenicities were studied in male F344/DuCrj rats by subcutaneous injection. Sarcomas, mainly malignant fibrous histiocytomas at the site of injection were induced in 8 to 17 (47%) rats by 1-nitropyrene and in 4 of 10 (40%) rats by 3-nitrofluoranthene. Some tumors were serially transplantable in the same strain of rats.

Air Pollutants↗
PubMed1982

Carcinogenicity test of quercetin and rutin in golden hamsters by oral administration.

Quercetin and its glycoside, rutin were tested for carcinogenicity in non-inbred golden hamsters of both sexes. In Experiment I, 10% quercetin, 10% rutin, or control diet was given to animals for 735 days. In this experiment, tumors appeared mainly in the forestomach, but the incidence was not statistically different among the three groups. Quercetin and rutin were not carcinogenic under these conditions. In Experiment II, Group 1 was given 4% quercetin diet for 709 days. Group 2 was given 1% quercetin diet for 351 days and then the basal diet for 350 days. Group 3 was given 1% quercetin diet and then 1% croton oil diet and Group 4 was given the basal diet followed by 1% croton oil diet, for the same periods as Group 2. Group 5 was given the basal diet for 701 days. In Experiment II, papillomas of the forestomach appeared in Groups 1, 2, and 5, and papillomatosis in Group 3 and 4. There were no statistical differences among experimental groups and respective controls. Thus, quercetin was not carcinogenic when given at the concentrations of 4% and 1%; even with the administration of 1% croton oil after 1% quercetin, there was no increase in tumor incidence.

Administration, Oral↗
PubMed1982

Genetic control of sensitivity of rats to gastrocarcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine.

The administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water induces tumours, mainly adenocarcinomas in the glandular stomach of rats. The sensitivities of different strains of rats to gastrocarcinogenesis induced by MNNG vary: Wistar and ACI strains are sensitive, whereas the Buffalo strain is resistant. Genetic analyses were made on the induction of gastric tumous by MNNG in the ACI and Buffalo strains and their F1 and F2 hybrids. Rats of both sexes, 7-9 weeks old, were given 83 micrograms of MNNG/ml of drinking water for 32 weeks and sacrificed in experimental week 72. The incidences of gastric tumours were as follows: ACI strain, male 80%, female 63%; Buffalo strain, male 29%, female 6%; F1 hybrid, male 35%, female 9%; F2 hybrid, male 65%, female 29%. There were no significant differences in the sensitivities of Buffalo X ACI F1 and ACI X Buffalo F1, or of Buffalo X ACI F2 and ACI X Buffalo F2. These results show that the gene(s) controlling resistance to MNNG is autosomal in the Buffalo strain and is inherited dominantly by F1 and F2 hybrids. In both strains and their hybrids, the incidence of gastric tumours was higher in males than in females.

Adenocarcinoma↗
PubMed1982

Mechanism of appearance of mutagenicity of N-nitrosodiphenylamine with norharman.

The mutagenicity of the carcinogen N-nitrosodiphenylamine (NDPhA) to Salmonella typhimurium TA98 was demonstrated only when norharman, a comutagen, was added to the incubation mixture with S9 mix. N,N-Diphenylamine (DPhA), a denitrosated derivative of NDPhA, was also mutagenic to S. typhimurium TA98 when norharman was present. Twice as many revertants were induced by DPhA with norharman as by NDPhA with norharman. The comutagenic effect of norharman was also observed with N-nitroso-methylphenylamine (NMPhA), N-nitrosoethylphenylamine (NEPhA) and N-nitrosophenylbenzylamine (NPhBeA) and their denitrosated derivatives. NDPhA was converted metabolically to DPhA by S9 mix. Stoichiometric studies indicated that the mutagenicity of NDPhA in the presence of norharman was exerted through DPhA. The denitrosation eyzme activity of NDPhA was mainly recovered in the microsomal fraction, and the enzyme seemed to be a cytochrome P-450 monooxygenase system. Denitrosation reactions of NMPhA, NEPhA and NPhBeA were also demonstrated. The mutagenicities of these compounds with norharman are therefore suggested to be due to a mechanism similar to that of NDPhA with norharman.

Alkaloids↗
PubMed1982

Genetic study of host factors in gastrocarcinogenesis in rats.

The effects of genetic factors on gastrocarcinogenesis in rats were studied by giving 83 micrograms/ml of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking-water to ACI strain rats, Buffalo strain rats, and their F1 hybrid rats for eight months. Animals were sacrificed on the 505th experimental day and examined histologically. The incidences of gastric carcinoma were as follows (no. of carcinoma-bearing rats/no. of effective animals): ACI rats, 86% (12/14) of males and 53% (9/17) of females; Buffalo rats, 19% (3/16) of males and 0% (0/13) of females; F1 hybrids between ACI and Buffalo rats, 23% (7/30) of males and 3% (1/32) of females. The incidence of gastric carcinoma in F1 hybrids was significantly lower than that in ACI rats but not significantly different from that in Buffalo rats. These results suggest that resistance to gastrocarcinogenesis by MNNG is an autosomally dominant trait.

Animals↗
PubMed1981

Carcinogenicity in mice of mutagenic compounds from a tryptophan pyrolyzate.

The compounds 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole, which are potent mutagens in a tryptophan pyrolyzate, ar hepatic carcinogens when given orally to mice at concentrations of 200 parts per million in a pellet diet. Female mice showed higher susceptibilities to both compounds than male mice.

Animals↗
PubMed1981

Co-mutagenic effect of norharman with N-nitrosamine derivatives.

The mutagenicities of 14 nitrosamine compounds were tested on Salmonella typhimurium TA98 and TA100 in the presence of the co-mutagen norharman. N-Nitrosophenyl compounds, such as N,N-diphenylnitrosamine, N-methyl-N-phenylnitrosamine, N-ethyl-N-phenylnitrosamine and N-phenyl-N-benzylnitrosamine, were mutagenic when norharman was added to the incubation mixture, but not mutagenic in its absence. Norharman did not enhance the mutagenic activities of N-nitrosoaliphatic compounds.

Alkaloids↗
PubMed1981

Liver cancer and precancerous changes in rats induced by the basic fraction of tryptophan pyrolysate.

The basic fraction of a tryptophan pyrolysate (Trp-P-BF) was given orally to Wistar rats for about 2 years. In Experiment I, 5 male rats each were given 0.2, 0.4, 0.6 and 0.8% Trp-P-BF. Dose-dependent growth retardation was observed in these groups and neoplastic nodules were found in the liver of 1 rat given 0.2% Trp-P-BF and a hepatocellular carcinoma was found in 1 rat given 0.4% Trp-P-BF diet. In Experiment II, 25 rats of both sexes were fed 0.5% or 0.2% Trp-P-BF diet. Neoplastic nodules were induced in 2 of 22 males and 5 of 18 females given 0.2% Trp-P-BF diet. Mammary adenomas developed, but no neoplastic nodules were found in the liver of rats fed on 0.05% Trp-P-BF or control diet. Females were more sensitive to Trp-P-BF than males.

Adenoma↗
PubMed1981

Maintenance by saccharin of membrane alterations of rat bladder cells induced by subcarcinogenic treatment with bladder carcinogens.

Saccharin is known to have a tumor-promoting effect on bladder cancer in rats, but its mechanism of action is unknown. We demonstrated that the increased agglutinability of isolated epithelial cells of the bladder in the presence of concanavalin A caused by a subcarcinogenic dose of bladder carcinogens disappeared shortly after the end of their administration. However, saccharin maintained the increased agglutinability when given continuously after administration of carcinogen. Moreover, the agglutinability of bladder cells previously exposed to a subcarcinogenic dose of bladder carcinogens increased again when saccharin was given after the agglutinability had disappeared completely.

Animals↗
PubMed1980

Sequential studies on the histopathogenesis of gastric carcinoma in rats by a weak gastric carcinogen, N-propyl-N'-nitro-N-nitrosoguanidine.

Sequential studies were made on the histopathologic changes in the glandular stomach of rats induced by a weak carcinogen. N-propyl-N'-nitro-N-nitrosoguanidine (PNNG). Fiftyfour rats were given 100 micrograms/ml of PNNG in their drinking water for 44 weeks, and then normal tap water until the end of the experiment. Rats were killed at intervals between week 1 and week 88. No marked atrophy or ulceration of the mucosa was found between week 1 and the end of the experiment. Focal intestinal metaplasia was found in week 19 and its incidence increased during the experiment. Adenocarcinoma in situ with extreme cellular atypia was found in mucosa with a normal appearance in week 67. An adenocarcinoma invading the submucosa was found in week 69, and one invading the serosa in week 88. All these pathological lesions were found on the anal side of the pyloric region. No pathologic changes were found in the fundic region. The sequential changes of the mucosa of the glandular stomach induced by this weak gastric carcinogen, PNNG, were very different from those induced by the potent gastric carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Gastric carcinoma induced by PNNG seems to be more similar to human gastric cancer than that induced by MNNG.

Adenocarcinoma↗
PubMed1980

Induction of sister-chromatid exchanges by mutagens from amino acid and protein pyrolysates.

Sister-chromatid exchanges (SCEs) in a permanent cell line of human lymphoblastoid cells were induced by 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]-indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-9H-pyrido[2,3-b]indole (2-amino-alpha-carboline). The first two compounds were found in tryptophan pyrolysates, the third in a glutamic acid pyrolysate and the last in a globulin pyrolysate. All these compounds required the metabolic activation system (S9 mix) for induction of SCE. Trp-P-2 had the highest SCE-inducing activity of these chemicals (approximately equivalent to that of aflatoxin B1), followed by Trp-P-1, Glu-P-1 and then 2-amino-alpha-carboline.

Carbolines↗
PubMed1980

Induction of 8-azaguanine or ouabain resistant somatic mutation of Chinese hamster lung cells by treatment with tryptophan products.

The basic fraction of tryptophan pyrolysis products (TBF) showed strong mutagenic activity on somatic cells of the lung of Chinese hamsters. In this somatic mutation test, TBF was demonstrated to have 5.6 times higher mutagenicity than diethylnitrosamine (DEN) when mutants were selected with 8-azaguanine, and 13.5-fold higher mutagenicity than DEN when mutants were selected with ouabain. From these findings, it is suggested that pyrolyzates of amino acids may have mutagenic actions on somatic cells of animals, as well as carcinogenic actions.

Animals↗