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Biomedical subjects

K Imaida

Publications and source records attributed to K Imaida.

192 records · Page 11Linked to original sources
PubMed1980

Effect of cyclophosphamide on rat urinary bladder epithelium treated wtih N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of cyclophosphamide (CP) on the urinary bladder epithelium of rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined histologically to detect preneoplastic papillary or nodular hyperplasia. The urinary bladder epithelium of rats injected intraperitoneally with 40 or 80 mg/kg body weight of CP after treatment with 0.025% BBN for 2 weeks showed extensive epithelial erosion and then simple, or papillary or nodular hyperplasia, but this soon almost disappeared. In contrast, rats given BBN alone showed papillary or nodular hyperplasia later. These findings indicate that epithelial damage by CP inhibited the early neoplastic process of BBN.

Animals↗
PubMed1980

The effects of various chemicals on the development of hyperplastic liver nodules in hepatectomized rats treated with N-nitrosodiethylamine or N-2-fluorenylacetamide.

The effects of various hepatocarcinogenic, non-hepatocarcinogenic and non-carcinogenic chemicals on the induction of hyperplastic liver nodules by N-nitrosodiethylamine (DEN) or N-2-fluorenylacetamide (2-FAA) as an initiator were studied in male Fischer 344 rats. Rats were injected intraperitoneally with 200 mg of DEN/kg body weight or were fed on basal diet containing 200 ppm of 2-FAA for 2 weeks, and then given various test chemicals starting from week 3. They were also partially hepatectomized in week 3. All animals were killed at the end of week 8 and examined histologically. For quantitative analysis, hyperplastic nodules in the liver were measured with a color video image processor, VIP-21C. The effect of various chemicals in rats treated with DEN or with 2-FAA were compared. The production of hyperplastic liver nodules was greatest in rats treated with strong hepatocarcinogens, and less in rats treated with weak hepatocarcinogens. Very few hyperplastic nodules were produced after treatment with non-hepatocarcinogens or noncarcinogens. Hyperplastic nodules were formed in rats treated with phenobarbital, which is a hepatopromoter. Saccharin, which is a urinary bladder promoter, did not enhance the production of hyperplastic nodules in the liver. These results indicate that many hepatocarcinogens enhance liver carcinogenesis. The classification of chemicals as liver carcinogens is discussed on the basis of the results.

2-Acetylaminofluorene↗
PubMedDate not supplied

Quantitative analysis of initiating and promoting activities of five mycotoxins in liver carcinogenesis in rats.

The initiating and promoting activities of several mycotoxins were investigated in F344 male rats. N-2-Fluorenylacetamide (2-FAA) was used as an initiator or a promoter and citrinin, ochratoxin A, sterigmatocystin, (+)rugulosin or patulin was administered at a fixed dose for the same period in the initiation stage or the promotion stage. Partial hepatectomy and administration of carbon tetrachloride (CCl4) were examined to increase the induction of hyperplastic nodules. Ochratoxin A, sterigmatocystin and (+)rugulosin administered in either the initiating or the promoting stage significantly increased the induction of hyperplastic nodules. Citrinin and patulin administered in the initiating stage significantly increased the induction of hyperplastic nodules, but were not effective when administered during the promoting stage. The theoretical classification of the mycotoxins examined is discussed.

Animals↗
PubMedDate not supplied

Effects of pesticide mixtures at the acceptable daily intake levels on rat carcinogenesis.

Possible modifying effects of pesticide mixtures on tumorigenesis were investigated with medium-term carcinogenesis protocols for rapid detection of carcinogenic agents using male F344 rats. In the 8-wk liver model, administration of 20 pesticides (19 organophosphorus compounds and one organochlorine), added to the diet each at acceptable daily intake (ADI) levels, did not enhance rat liver preneoplastic lesion development initiated by diethylnitrosamine. In contrast, a mixture of these 20 pesticides at 100 times the ADI significantly increased the number and area of liver lesions. In the second experiment using a multi-organ carcinogenicity protocol of 28 wk, mixtures of 40 pesticides (high production examples) or 20 pesticides (suspected carcinogens) added to the diet at their respective ADI levels did not modulate carcinogenesis in any organ initiated by five known potent carcinogens in combination. These results thus provide direct support for the safety factor (usually 100) approach using ADI values for the quantitative risk evaluation of pesticides.

Administration, Oral↗
PubMedDate not supplied

Establishment of an animal model for pulmonary fibrosis in mice using monocrotaline.

A preliminary attempt at experimental induction of pulmonary fibrosis in which male ICR mice received 15 weekly sc injections of 200 or 100 mg/kg monocrotaline (MC) revealed that most animals treated with the larger dose died of severe interstitial pneumonia, whereas those given 100 mg/kg exhibited only relatively slight lung injury. Based on these results, male mice were administered sc injections of 200 and 100 mg/kg MC once a week for 9 and 18 times, respectively, and then maintained without any further treatment until week 28 after the start. Mice treated with 200 mg/kg MC showed severe pulmonary damage and died by week 25. Mortalities also occurred in the 100-mg group from week 16, with 11 of 40 animals surviving at the termination of the experiment. Histologically, both dose groups demonstrated severe interstitial pneumonia and/or pulmonary fibrosis. Ultrastructurally, inflammatory edema possibly attributable to injuries of alveolar capillary endothelial cells was observed in the high-dose group at week 8, and there was a remarkable increase in collagen fibers in alveolar septa in this group thereafter. The present study results suggest that lung injuries induced by MC treatment progress to irreversible lung fibrosis and that this animal model may have advantage for studying the pathogenesis of lung cancers in patients with pulmonary fibrosis.

Animals↗
PubMedDate not supplied

Chronic administration of the mutagenic heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine induces cardiac damage with characteristic mitochondrial changes in Fischer rats.

Fischer-344 rats of both sexes were administered the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) for 52 wk at the dietary level of 400 ppm. Light microscopic and ultrastructural investigation of the myocardium revealed prominent changes in all PhIP-treated male and female animals investigated. These were characterized by a diffuse proliferation of markedly enlarged mitochondria, with abundant cristae and often containing lamellar bodies as inclusions. PhIP is well known to cause DNA adducts in the rat heart, and there are numerous reports of mutations in mitochondrial DNA in both humans and experimental animals being associated with very similar lesions to those observed in the present study. The results thus suggest that this heterocyclic amine induces cardiac damage by the same mechanism.

Animals↗
PubMedDate not supplied

Marriage of a medium-term liver model to surrogate markers--a practical approach for risk and benefit assessment.

The need for a reliable medium-term alternative to traditional long-term rodent test protocols for carcinogen risk assessment is pressing given the immense variety of compounds being developed for introduction into the human environment. The established lack of a complete correlation between mutagenicity and carcinogenicity means that recourse must be made to an in vivo model. Optimally, this model should be able to detect not only complete carcinogenic or promoting potential but also any ability to inhibit neoplasia. In order to be effective, it must take into account the available detailed knowledge on mechanisms of action of carcinogens and modulating agents. The Ito model, for which a uniquely comprehensive set of background data has already been accumulated, has a solid scientific basis; this model utilizes quantitative data for glutathione S transferase-positive foci as the preneoplasia-based surrogate end point (PSE). A very practical candidate for routine application, its predictive power, its flexibility, and its capacity to incorporate a range of mechanism-based surrogate end points (MSEs) provide a powerful tool for attainment of the twin goals of detecting carcinogenic agents and identifying promising chemopreventors.

Animals↗
PubMedDate not supplied

Anophthalmia in litters of female rats treated with the food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Anophthalmia in litters of pregnant rats treated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a food-derived carcinogen, was incidentally encountered in a risk-assessment study with 2-generation exposure to PhIP. Female Fischer 344 animals were given 200 ppm PhIP in the diet for 4 wk before mating with nontreated males and also during gestation and lactation periods. Mean numbers of newborn rats per litter in control and PhIP-treated groups were 7.9 +/- 2.9 and 7.1 +/- 1.6 in trial 1 and 8.3 +/- 1.9 and 6.1 +/- 2.4 in trial 2. Among 49 (trial 1) and 63 (trial 2) offspring from PhIP-treated dams, 9 (18.4%) and 32 (50.8%) demonstrated anophthalmia, and 1 (2.0%) and 8 (12.7%) demonstrated hydrocephaly. Five of 7 (71.4%) and 13 of 14 (92.9%) dams delivered pups with malformations in trials 1 and 2, respectively. Also, in a previous study that was carried out with the same protocol and that used the Sprague-Dawley strain of rats, anophthalmia and hydrocephaly were observed in 2 and 1 out of 175 pups, respectively, from 100 ppm PhIP-treated dams. No congenital malformations were found in control groups of the same size in either experiment. In addition to having been previously identified as a cause of carcinogenic activity, our findings suggest that PhIP is capable of causing anophthalmia in rats when administered during the gestational period.

Animals↗
PubMedDate not supplied

Modifying effects of phytic acid and gamma-oryzanol on the promotion stage of rat carcinogenesis.

The modifying effects of phytic acid and gamma-oryzanol on the promotion stage of carcinogenesis were investigated using several two stage carcinogenesis models in rats. In a multi-organ carcinogenesis model, male F344 rats were given combined treatment with 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN), N-ethyl-N-hydroxyethylnitrosamine (EHEN) and 3,2'-dimethyl-4-aminobiphenyl (DMAB) during the initial 3 weeks as initiators, and then treated with dietary 2% phytic acid (50% in water), 1% gamma-oryzanol or basal diet alone for 32 weeks. Although the appearance of hepatic tumors was suppressed, the incidence of urinary bladder papillomas was increased by phytic acid. In addition, the incidence and multiplicity of lung tumors were significantly increased by gamma-oryzanol. Esophagus, colon, pancreas, kidney and thyroid lesion development was not influenced by these compounds. In a gamma-oryzanol dose response experiment using DHPN in the drinking water as an initiator, enhancing effects on lung were observed at a dose of 1% but not at 0.5% or lower. When the modifying effects of phytic acid, and its sodium (Na-PA), potassium (K-PA) and magnesium (Mg-PA) salt were further examined in rats pretreated with the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), a clear increase in the incidences of bladder tumors was noted, with only Na-PA, phytic acid itself being without effect. Finally, examination of the modifying potential of phytic acid and gamma-oxyzanol on mammary carcinogenesis in female Sprague Dawley rats pretreated with a single intragastric dose of 7,12-dimethylbenz(a)anthracene (DMBA) revealed no significant differences in the final incidences and multiplicities of mammary tumors, but the average tumor diameter was significantly reduced and the average survival time was increased with phytic acid. gamma-Oryzanol tended to decrease the size of the tumor but without significant difference. These results indicate that phytic acid inhibits hepatic and mammary carcinogenesis, while its Na-salt is a promoter of bladder carcinogenesis. The effect of phytic acid itself on urinary bladder carcinogenesis is equivocal. gamma-Oryzanol is a promoter of lung carcinogenesis but its effect is weak and exerted only at a very high dose level.

9,10-Dimethyl-1,2-benzanthracene↗