Biomedical subjects

K Imaida

Publications and source records attributed to K Imaida.

At least 91 records · Page 5Linked to original sources

PubMed1992

Induction of colon adenocarcinomas in CD rats and lung adenomas in ICR mice by 6-nitrochrysene: comparison of carcinogenicity and aryl hydrocarbon hydroxylase induction in the target organs of each species.

Species and organ specificity of 6-nitrochrysene (6-NC)-induced carcinogenicity and the potential correlation with aryl hydrocarbon hydroxylase (AHH) induction in the target organs were investigated in both sexes of ICR mice and CD rats. Animals received total 6-NC doses of 1.4 mumol/mouse and 14.8 mumol/rat. The first i.p. injection was performed within 24 h of birth, then the animals were subjected to 3 and 5 weekly injections in the mouse and rat cases, and the survivors were sacrificed at weeks 24 and 32, respectively. Adenocarcinomas and dysplasias and/or adenomas of the colon in rats and lung adenomas in mice were observed in animals treated with 6-NC. However, no such lesions were observed in animals treated with the vehicle dimethyl sulfoxide alone. AHH activities in the lung, colon, and liver of each animal after treatment with 6-NC or dimethyl sulfoxide were also investigated. Six-week-old animals received a single 6-NC injection i.p. at the dose of 0.8 mumol/mouse or 8.0 mumol/rat. Animals were sacrificed on day 1 or 7 following injections, when AHH levels were measured. The results indicated enzyme levels in all these organs to be elevated by 6-NC treatment, the induction rate in the mouse lung being the highest. These results showed that 6-NC is carcinogenic for the colon of rats, as well as the lung of mice, and that it also induces AHH activity in both target and nontarget organs.

Adenocarcinoma↗

PubMed1992

Lack of synergism among DMAB, BOP, and MNU in induction of carcinomas of the rat ventral prostate.

The present experiment was undertaken to investigate possible synergism in induction of rat prostate tumor. F344 rats were repeatedly administered the prostate carcinogens 3,2'-dimethyl-4-aminobiphenyl (DMAB),N-nitrosobis(2-oxopropyl)amine(BOP), and N-methylnitrosourea (MNU) sequentially or together at times of hormonal castration induced regenerative cell proliferation of prostate epithelial cells. Group 1 animals received two 100 mg/kg doses of DMAB, two 20 mg/kg applications of BOP, and two times 15 mg/kg of MNU. Groups 2, 3, and 4, respectively, received each of the carcinogen treatment alone. Group 5 was given 6 applications of all three in combination, each at one-third the dose administered to the other groups. The results showed a clear synergism in enhanced tumor development in the colon but not in the prostate, in which the incidence of lesions induced by the three carcinogens was similar to that with DMAB alone.

Aminobiphenyl Compounds↗

PubMed1992

Strategy of research for cancer--chemoprevention.

It has been reported that environmental chemicals are important factors in terms of both development and prevention of human cancer. For the latter, detection of early stages is an essential first step followed by clinical trials for surveying populations at risk. Thus a great deal of attention has been focused on these areas. However, investigations of possibilities for active prevention of cancer development itself form another major project. Chemoprevention of carcinogenesis, which means prevention of carcinogenesis by exogenous chemical compounds, has been investigated extensively in a variety of organs in animal models. Usually attention is concentrated on only one organ. However, antioxidants, such as BHA, exert very different effects on different organs, suggesting the necessity of whole body approaches to the question of chemoprevention. Furthermore, the mechanisms of chemoprevention, including the step of carcinogenesis, i.e., initiation, promotion, progression or whole carcinogenesis steps, in which exogenous compounds exert their protective effects, should be considered. A medium-term bioassay system and a multi-organ carcinogenesis system, which can be used for investigation of potential for cancer chemoprevention, have been developed in our laboratory. Dose dependent inhibitory effects were established for both BHA and alpha-tocopherol in the medium-term bioassay system, and inhibition of small intestinal carcinogenesis by catechins in green tea has also been investigated in our multi-organ carcinogenesis protocol. It is extremely important for prevention of human cancer that we find new candidates for chemopreventive agents using animal studies. This paper reviews published reports on chemoprevention, taking into account effective stages, and proposes suitable experimental animal models for future investigations in this increasingly important area.

Animals↗

PubMed1992

N-nitrosoheptamethyleneimine-induced pulmonary and esophageal carcinogenesis and effects of concomitant treatment with bleomycin in rats.

The combination effects of bleomycin with N-nitrosoheptamethyleneimine (NHMI) or dihydroxy-di-N-propylnitrosamine (DHPN) on pulmonary carcinogenesis were investigated. Male F344 rats were given NHMI (20 or 40 ppm) or DHPN (200 ppm) in the drinking water and intraperitoneally injected with bleomycin (1 mg/kg) once a week for 18 weeks and then killed at week 24. Many rats treated with NHMI died before the termination of the experiment due to toxicity or development of advanced esophageal carcinomas, considered to be the main cause of death. Detailed histological examination performed on rats killed at week 24 revealed no statistically significant effects of bleomycin on NHMI or DHPN induction of neoplastic lesions in the lung or esophagus, although pulmonary carcinomas were only found in two rats treated with NHMI plus bleomycin. Under the present experimental conditions, NHMI exerted stronger carcinogenic activity in the esophagus than in the lung, and no obvious modifying effects of simultaneously administered bleomycin were evident on NHMI- or DHPN-induced pulmonary carcinogenesis.

Adenoma↗

PubMed1992

Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (OECD): familiarization using cyclophosphamide.

A familiarization study was conducted on the "Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)" proposed by the OECD. Cyclophosphamide (CP) at doses of 6.7, 4.5, 3, 2, and 0 mg/kg body wt was given daily by gavage to groups of 12 male and 12 female Sprague-Dawley rats. As a result, anemia and leukopenia were evident in treated males. The absolute and relative thymus and spleen weights were decreased in treated rats. Histopathologically, atrophy of the thymus, spleen, and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss of fetuses and postnatal death were found in dams given CP. The body weight of pups treated with CP was significantly lowered in a dose-related manner. Thus the results demonstrated most of the known toxicological properties of CP, except the adverse effects on spermatogenesis and fertility. Therefore ReproTox can be considered as a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume.

Animals↗

PubMed1992

Pathological markers for non-genotoxic agent-associated carcinogenesis.

A variety of positive or negative enzyme altered foci have been proposed as preneoplastic marker lesions in the rat liver. Frozen sections are required in some cases. We have compared the suitability of various histochemically or immunohistochemically demonstrated markers and concluded that immunohistochemically-stained glutathione S-transferase placental form (GST-P) positive foci are particularly useful for practical application in risk assessment. Advantages include ease of quantitative foci analysis on a number of samples since acetone or formalin-fixed paraffin blocks can be used and clear contrast of foci against the surrounding liver tissue facilitates recognition. We have established a liver medium-term bioassay model of 8 weeks' duration using diethylnitrosamine as an initiator and GST-P positive foci as the endpoint lesions. At present, 58 non-genotoxic chemicals for which carcinogenicity data are available have been examined and many carcinogenic agents, mostly liver carcinogens, have been satisfactorily detected as having carcinogenic potential. Exceptional examples are two peroxisome proliferators, clofibrate and DEHP. For these chemical, several peroxisomal enzymes such as catalase and enoyl CoA hydratase have been tested as markers.

Animals↗

PubMed1992

Correlation between cataract and retinopathy due to lighting in F344 rats used in a long-term carcinogenicity study.

Correlations between light intensity of animal room lighting and both cataract and retinopathy of rats were examined, and relationships between the cataract and the retinopathy were further investigated. Seventy-nine male rats and 106 female rats surviving to the end of a 2-yr carcinogenicity study of monosodium succinate were used in this investigation. Animals were housed in polycarbonate cages, each containing 4 rats, with wire lids and hardwood chips for bedding and with a 12-h light/dark cycle. Individual groups comprising 13 cages were inserted into 3 by 5 cage hanging type racks. Light intensity was measured at the bottom (on the bedding) of individual cages. Statistically, both the incidence of cataracts and the severity of retinopathy were closely related to light intensity. The incidence of cataracts in males was significantly higher than that in females, while no sex difference was observed for the severity of retinopathy. Meanwhile, no differences in either the incidence of cataracts or the severity of retinopathy were observed between the monosodium succinate-treated and control groups and between the right and left eyes. While the occurrences of retinopathy and cataract were strongly associated, our results indicated that retinopathy occurs more frequently than cataracts, and thus the retina appeared to be more sensitive to the effects of lighting.

Animals↗

PubMed1992

Inhibitory effects of crude soybean trypsin inhibitor on pancreatic ductal carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine.

The effects of soybean trypsin inhibitor (SBTI) administration during the promotion phase of pancreatic carcinogenesis were investigated. Female Syrian golden hamsters were given three weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine (BOP) each at a dose of 10 mg/kg and then administered 5% SBTI diet for the following 37 weeks. Additional groups of animals received the BOP injection alone or the 5% SBTI diet alone as controls. At week 40 of the experiment, all surviving animals were killed and development of pancreatic lesions was assessed histopathologically. The results showed that the incidence of dysplastic lesions in hamsters of the BOP/SBTI group was significantly decreased as compared to that of the BOP group (P < 0.01). A similar but not significant tendency was also found for pancreatic adenocarcinomas. In addition, the number of dysplastic lesions in the pancreas head portion in the BOP/SBTI group were significantly decreased as compared to the BOP group value (P < 0.05). Furthermore, atrophic changes of the pancreatic exocrine tissue were more severe in the BOP group than in the BOP/SBTI group (P < 0.01), indicating that SBTI treatment gave effective protection against the replacement process of acinar cell induced by BOP. Thus, the present experiment demonstrated that SBTI can inhibit hamster pancreatic ductal carcinogenesis when given in the promotion phase, in clear contrast to the enhancing effects reported for preneoplastic acinar lesion development in rats.

Animals↗

PubMed1992

Promoting effects of cigarette smoke on the respiratory tract carcinogenesis of Syrian golden hamsters treated with diethylnitrosamine.

The potential short-term promoting effects of cigarette smoke on the development of tumors in the respiratory system were investigated in male Syrian golden hamsters. Three groups (1, 2 and 3) of 30 animals each received a single s.c. injection of 100 mg/kg body wt of diethylnitrosamine (DEN) at the commencement of experiment 1. They were then exposed to non-filter cigarette (NC) smoke, filter-tip cigarette (FC) smoke and sham smoke respectively, in a Hamburg II type smoking machine from week 1 to week 12. In addition, groups 4, 5 and 6 (10 animals each) were exposed to the NC smoke, FC smoke or sham smoke respectively, for the same time period without prior DEN treatment. In the DEN-treated groups, epithelial hyperplasias and/or papillomas were induced, the incidences and numbers/animal of these lesions in groups 1 and 2 being significantly increased as compared to group 3 values. In experiment 2, two groups of 25 hamsters each were exposed to cigarette smoke or sham smoke for up to 12 weeks, five animals in each group being killed for immunohistochemical analysis using BrdU antibodies and measurement of lipid peroxides in the lung and serum at weeks 1, 2, 4, 8 and 12. Small aggregations of macrophages (smoke cells) in the lung alveoli was observed in the smoke-exposed group, but no significant increase in the numbers of BrdU positive cells in any compartment of the respiratory system was apparent. Animals of this group showed a tendency for increased lung malondialdehyde levels at weeks 2 and 12, but not weeks 4 and 8.

Animals↗

PubMed1992

Suppression of spontaneous hepatocellular carcinoma development in C3H/HeNCrj mice by the lipophilic ascorbic acid, 2-O-octadecylascorbic acid (CV-3611).

The study was performed to examine the effects of the lipophilic ascorbic acid, 2-O-octadecylascorbic acid (CV-3611), with a strong scavenging capacity for active oxygen species, on the spontaneous development of liver tumors in male C3H/HeNCrj mice. Animals were given a diet containing 0.1% CV-3611 for a total experimental period of 16 months. Hepatocellular carcinomas developed in 2/39 (5%) of these experimental mice and in 11/43 (26%) of control mice fed a basal diet. The numbers of carcinoma per mouse were 0.05 +/- 0.22 and 0.33 +/- 0.61 respectively. Thus, CV-3611 clearly suppressed the development of hepatocellular carcinomas. However, the scavenger did not affect either the incidence or the number of hepatocellular adenomas, suggesting that active oxygen species might be involved in the conversion of adenomas to carcinomas in spontaneous liver carcinogenesis in C3H/HeNCrj mice.

Animals↗

PubMed1992

Induction of pancreatic tumors in male Syrian golden hamsters by intraperitoneal N-methyl-N-nitrosourea injection.

The carcinogenic effects of N-methyl-N-nitrosourea (MNU) in male Syrian golden hamsters were investigated. After single i.p. administration of MNU at doses of 50 mg/kg or 10 mg/kg, or after five fractionated i.p. injections to make a total dose of 50 mg/kg body weight (10 mg x 5), histopathological examinations were performed at the end of 40th week of the experiment. Neoplastic changes were observed in various organs, and lesions in the pancreas, forestomach, and adrenal gland were predominant. In the pancreas, three tumor types were observed: ductal adenocarcinomas, acinar cell carcinomas, and islet cell carcinomas. The incidences of pancreatic ductal carcinomas were 56, 27, and 0% in the single 50-mg, fractionated 50-mg, and single 10-mg groups, respectively. Two islet carcinomas were observed in the single 50-mg group, and an islet carcinoma and an acinar cell carcinoma were also observed in the fractionated 50-mg group. Several miscellaneous neoplastic lesions, including squamous cell papillomas/carcinomas in the forestomach, cortical adenomas in the adrenal glands, and a seminoma in the testis were also observed. These results indicate MNU to be a multipotent carcinogen with the pancreas as a target organ in the Syrian golden hamster under this experimental condition. The observed high induction rate for pancreatic ductal carcinoma suggests that this MNU protocol is a useful candidate model for experimental pancreatic ductal carcinogenesis.

Animals↗

PubMed1992

Dose dependence of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl-induced rat prostate carcinogenesis.

Groups of F344 rats were administered biweekly intraperitoneal injections of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl (N-OH-DMAB) at a dose of 5, 10 or 20 mg/kg body weight or DMAB, the parent compound, at a dose of 25 mg/kg body weight, for a total of 10 times. Prostate carcinomas in the ventral lobe developed in a N-OH-DMAB dose-dependent manner (0, 17.6 and 66.7%, respectively) with limited tumor yields in other organs. Although intraperitoneal administration of DMAB was similarly found to induce prostate tumors, it also caused severe chemical peritonitis, which resulted in a high mortality. The present data confirmed that intraperitoneal administration of N-OH-DMAB provides a relatively specific induction method for models of prostate carcinogenesis.

Aminobiphenyl Compounds↗

PubMed1992

Induction of adenocarcinomas in the glandular stomach of BALB/c mice treated with N-methyl-N-nitrosourea.

Male 6-week-old BALB/c strain animals (groups 1 and 2) received 10 weekly intragastric intubations of 0.5 mg/mouse of N-methyl-N-nitrosourea. At week 11 the forestomachs were resected in group 1 but not group 2. Although many animals in group 2 died due to development of squamous cell carcinomas in the forestomach, development of cancers in the glandular stomach was quite similar in both groups. Well-differentiated adenocarcinomas in groups 1 and 2 were found at low incidence at week 20, rising to 100% at week 40, with two lesions metastasizing to the lymph nodes. Four poorly differentiated adenocarcinomas and 5 signet ring cell carcinomas were also found in 27 glandular stomach tumor-bearing animals.

Adenocarcinoma↗

PubMed1992

Modifying effects of soybean trypsin inhibitor on development of eosinophilic nodules and basophilic foci in the exocrine pancreas of male Sprague-Dawley rats treated with 4-hydroxyaminoquinoline 1-oxide.

Administration of 4-hydroxyaminoquinoline 1-oxide (HAQO) to rats results in development of 2 types of pancreatic acinar lesions, namely eosinophilic nodules and basophilic foci. To cast light on the biological character of these lesions, 5-week-old male Sprague-Dawley rats were given a single intravenous injection of HAQO at a dose of 7 mg/kg and, thereafter, fed soybean trypsin inhibitor (SBTI) at dose levels of 10% and 5%. At week 57, all rats were killed for pathological examination of pancreatic tissue. The incidence of eosinophilic nodules was significantly higher in the HAQO/SBTI group than in the HAQO-alone group, whereas the basophilic acinar foci were observed to occur less frequently and to be smaller in the HAQO/SBTI-treated animals. Administration of SBTI is known to increase the blood level of cholecystokinin, a trophic factor for pancreatic acinar cells. Thus, the present findings suggest that long-term elevation of this endocrine factor can affect the two types of pancreatic acinar lesions in essentially different ways, namely enhancing development of eosinophilic nodules, while suppressing the occurrence of basophilic foci.

4-Hydroxyaminoquinoline-1-oxide↗

PubMed1992

[Twenty-eight-day repeated dose toxicity test of pentaerythritol in F344 rats].

A twenty-eight-day repeated dose toxicity test of pentaerythritol at dose levels of 1000 or 0 mg/kg/day was carried out in male and female F344 rats. Thirteen animals of each sex were divided into 2 groups with 7 rats receiving pentaerythritol treatment and 6 rats served saline as control. All groups received an i.g. administration daily for 28 days. As to serum biochemical and hematological examinations, there were no serious differences between the pentaerythritol-treated rats and the control rats. On histopathological examination, no specific changes were observed in the pentaerythritol-treated rats. Based on these results, the no-observed-effect level of pentaerythritol can be concluded to be more than 1000 mg/kg/day.

Administration, Oral↗

PubMed1992

Latent prostatic carcinomas found at autopsy in men over 90 years old.

Step-sections of 29 whole prostate glands obtained at autopsy from elderly men aged 90 years or over have been investigated. Latent prostatic carcinomas were found in 17 cases (58.6%), all in the peripheral region. The majority of these latent prostatic carcinomas in very old individuals were considered to correspond to stage A1 tumors since, in 75% of cases, the diameter was less than 1 cm. Benign nodular hyperplasia and atypical hyperplasia were also observed in 26 (89.7%) and 14 cases (48.3%), respectively. There was a clear correlation between the appearance of atypical hyperplasia and the presence of latent prostatic carcinoma.

Adenocarcinoma↗

PubMed1991

Comparative carcinogenicities of 1-, 2-, and 4-nitropyrene and structurally related compounds in the female CD rat.

The comparative carcinogenicities of N-hydroxy-N-acetyl-1-aminopyrene, N-acetyl-1-aminopyrene, and 1-, 2-, and 4-nitropyrene were determined following i.p. injection into weaning female CD rats (67 mumol/kg body weight in dimethyl sulfoxide; 3 times/week for 4 weeks). At sacrifice 61 weeks after the first injection the incidences of malignant mammary tumors were increased significantly to 45 and 24% in the 4-nitropyrene- and N-hydroxy-N-acetyl-2-aminofluorene-treated groups, respectively. Cellular altered foci in the liver were increased significantly in the N-acetyl-1-aminopyrene-, N-hydroxy-N-acetyl-1-aminopyrene-, and N-hydroxy-N-acetyl-2-aminofluorene- treated groups; the latter two compounds also led to significantly increased formation of hyperplastic nodules in this organ. Significant increases in leukemia induction were observed in animals treated with 2-nitropyrene or N-hydroxy-N-acetyl-2-aminofluorene. In an experiment designed to compare the influence of the route of administration on the carcinogenic potential of this agent, 1-nitropyrene was injected i.p. or s.c. into weanling female CD rats (100 mumol/kg body weight; once a week for 4 weeks). The animals were sacrificed at 87 to 90 weeks after the first treatment. The incidences of mammary gland tumors in animals receiving injections of 1-nitropyrene by either route (59%) were significantly higher than in solvent-injected controls (37%). The incidences of adenocarcinoma in the i.p. 1-nitropyrene group (28%) and fibroadenoma in the s.c. 1-nitropyrene group (52%) were significantly higher than in the control animals (7 and 27%, respectively). These data suggest that the demonstration of the weak carcinogenicity of 1-nitropyrene is probably more a function of the length of the observation period than of the routes of administration used here. A further exploration of the effect of the route of administration involved treatment of weanling female CD rats by direct injection of 1-, 2-, or 4-nitropyrene into the mammary fat pads. A total of 2.04 mumol of the nitrocompound in dimethyl sulfoxide was injected into the mammary glands under each of the 6 left nipples. The right mammary glands were treated with the solvent only. Injections of the thoracic nipple areas were carried out on day 1; inguinal areas were treated on day 2. The animals were sacrificed after 77 weeks. The number of mammary tumor-bearing animals (23 of 28), the number with fibroadenoma (15 of 28), and the number with adenocarcinoma (19 of 28) were significantly increased in the 4-nitropyrene-treated group as compared with animals treated with only dimethyl sulfoxide.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

PubMed1991

Lack of carcinogenicity of 2-aminofluorene, its glucuronide and the glucuronide of N-hydroxy-2-acetylaminofluorene in heterotopic bladder of the rat.

The role of 2-aminofluorene and its N-glucuronide and the O-glucuronide of N-hydroxy-2-acetylaminofluorene in the bladder carcinogenesis by 2-aminofluorene were investigated. These compounds were injected into heterotopically transplanted bladders of male rats at a weekly dose of 1 mumol for 20 weeks. The experiment was terminated at the end of 50 weeks. The results showed that none of these compounds were carcinogenic in the heterotopically transplanted bladder. The O-glucuronide was not carcinogenic even when it was administered in a phosphate saline (pH 8.0), that favors the activation of this compound. The N-glucuronide of N-hydroxy-2-aminofluorene, a positive control, produced urothelial tumors. These results are consistent with the hypothesis that the N-glucuronides of hydroxylamines, but not the O-glucuronides of hydroxamic acids, are responsible for bladder carcinogenesis by arylamines.

Animals↗