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K Imaida

Publications and source records attributed to K Imaida.

At least 163 records · Page 9Linked to original sources
PubMed1986

[Evaluation of the carcinogenic risk of environmental chemicals].

Many carcinogens have been detected in our environment, and chemicals which have been shown to induce cancers in experimental animals have been largely eliminated. However, there are still many chemicals which have not been studied in rodent carcinogenicity tests. In this paper, we review the evaluation of carcinogenic risk of environmental chemicals to humans. Carcinogenic risk to humans is evaluated primarily in three different phases: carcinogenicity studies in animal experiments, in vitro short-term screening studies, and finally human epidemiological studies. There are 30 chemicals, processes or industries which have been subject to these three phases and determined to be carcinogenic to humans by the International Agency for Research on Cancer (IARC). Carcinogenic risk of chemicals should be evaluated quantitatively by their threshold doses, TD50 and virtually safe dose (VSD). Furthermore, the target organ of the carcinogen should also be taken into account, which has been emphasized by the demonstration of carcinogenicity of BHA in the forestomach of rats. Summational, synergistic, antagonistic and inhibitory effects of chemicals should also be discussed. It is important to establish a guideline for detecting and eliminating environmental carcinogens in order to prevent cancer in humans.

Animals↗
PubMed1985

Different responses to phenobarbital promotion in the development of gamma-glutamyltranspeptidase-positive foci in the liver of rats initiated with diethylnitrosamine, N-hydroxy-2-acetyl-aminofluorene and aflatoxin B1.

The promoting activities of phenobarbital (PB) on the development of gamma-glutamyl-transpeptidase-positive (gamma-GT+) foci in rat liver with three different initiating agents were compared in a short-term system (8 weeks). Male F344 rats were initiated by a single application of 200 mg/kg of diethylnitrosamine (DEN), 30 mg/kg of N-hydroxy-2-acetylaminofluorene (N-OH-AAF), 1.0 or 0.5 mg/kg of aflatoxin B1 (AFB1) or the vehicles alone. Two weeks after the initiation, animals were placed on a 0.05% PB diet for 6 weeks. Partial hepatectomy was performed at the end of the third week of the experiment. As a positive control, some animals were fed diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) after the initiation. The number and area of gamma-GT+ foci in the liver were quantified. All three initiators showed a summation effect with 3'-Me-DAB on the appearance of gamma-GT+ foci. Promotion by PB, however, was observed only in DEN-initiated rats and not in N-OH-AAF- or AFB1-initiated rats. It is apparent from the present experimental data that the promoting potential of PB on liver carcinogenesis depends on the initiating agent.

Aflatoxin B1↗
PubMed1984

Promoting effects of unilateral ureteric ligation on two-stage urinary bladder carcinogenesis in rats.

The effect of ligation of the left ureter on the development of lesions in the urinary bladder were investigated in male F344 rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for 2 weeks followed by 0.002% N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) for 10 or 22 weeks. The lesions of the urinary bladder found in weeks 12 and 24 in rats treated with BBN and EHBN were preneoplastic papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer. The incidences and numbers of these lesions per 10 cm of basement membrane of urinary bladder were increased significantly by ureteric ligation. Treatment with BBN or EHBN only induced no remarkable change and thus the doses used were subcarcinogenic in the conditions used. The results show that unilateral ureteric ligation enhanced two-stage bladder carcinogenesis.

Animals↗
PubMed1984

Modifying effects of butylated hydroxyanisole, ethoxyquin and acetaminophen on induction of neoplastic lesions in rat liver and kidney initiated by N-ethyl-N-hydroxyethylnitrosamine.

Studies were made on the effects of butylated hydroxyanisole (BHA), ethoxyquin (EQ) and acetaminophen (AAP) on the induction of neoplastic lesions in the liver and kidney of rats initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN). The number and area of histochemical gamma-glutamyltranspeptidase-positive (gamma-GT+) foci per unit area of liver section in rats given BHA, EQ or AAP were significantly less than in rats given EHEN alone. Similarly, the number of hyperplastic nodules (HN) in groups given BHA or AAP and their area in groups given BHA, EQ or AAP were significantly less than in control groups. Induction of hepatocellular carcinoma (HCC) was also clearly inhibited by these three chemicals. No liver lesions were found in any animals given BHA, EQ or AAP orally without EHEN. In contrast, the incidence and quantitative values of preneoplastic lesions and renal cell adenoma were significantly increased in groups given BHA, EQ or AAP. The results clearly demonstrated that BHA, EQ and AAP inhibited the development of gamma-GT+ foci, HN and HCC, whereas they enhanced the appearance of preneoplastic and neoplastic lesions in the kidney.

Acetaminophen↗
PubMed1984

Three-dimensional observations by scanning electron microscopy on the blood supply and organization of vasculature during hepatocarcinogenesis in rats.

Three-dimensional vascular changes in rats during hepatocarcinogenesis were studied by stereoscopic and scanning electron microscopic observation of vascular casts of sinusoids by injecting resin from hepatic artery (red color) and portal vein (blue color). Neoplastic lesions were synchronously induced by injection of diethylnitrosamine (DENA) followed by feeding of 2-acetylaminofluorene (2-AAF) plus partial hepatectomy, then periodically killed for examination. At 6 weeks after DENA injection sinusoids of hyperplastic foci (HF) were filled with blue resin similar to surrounding tissue, then at 8 weeks some HF and hyperplastic nodules (HN) took up red resin leaving surrounding sinusoids blue. At 12 to 18 weeks, red HN became more discrete with obvious compression of surroundings but decreased their number whereas blue HN were not. Red HN had incomplete anastomosing sinusoids giving a coral-like appearance. Spongy or cystic areas contained little or no resin, suggesting ischemic condition. Hepatocellular carcinomas (HCC) at 40 weeks took exclusively arterial red resin forming irregularly shaped anastomosing sinusoids. These findings indicate that acquisition of arterial blood supply by HF may relate to their further development to persistent HN and HCC.

2-Acetylaminofluorene↗
PubMed1984

Modification of carcinogenesis by antioxidants and other compounds.

Studies were made on the effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium L-ascorbate (SA), ethoxyquin (EQ) and acetaminophen (AAF) on the induction of neoplastic lesions in the liver, kidney or urinary bladder of rats initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN), diethylnitrosamine (DEN) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The number and area of histochemical gamma-glutamyltranspeptidase-positive (gamma-GT+) foci per unit area of liver section in rats given BHA, BHT, EQ or AAP, but not SA, were significantly less than in rats given EHEN or DEN alone. Similarly, the number of hyperplastic nodules (HN) in groups given BHA or AAP and their area in groups given BHA, EQ or AAP were significantly less than in control groups. Induction of hepatocellular carcinoma (HCC) was also clearly inhibited by these three chemicals. In contrast, the incidence and quantitative values of preneoplastic lesions and renal cell adenoma in the group given EHEN were significantly increased in groups given BHA, EQ or AAP administration. For assesing the influence of BHA and BHT on urinary bladder carcinogenesis, rats received BHA or BHT after treatment with BBN. The incidences and the number per unit length of basement membrane of papilloma and carcinomas were significantly increased in rats given BHA. BHT also showed significant increase but values were less than with BHA. These results clearly demonstrated that BHA, BHT, EQ and AAP inhibit the development of gamma-GT+ foci, or HN and HCC, whereas BHA, EQ and AAP enhance the appearance of preneoplastic and neoplastic lesions in the kidney, BHA and BHT also enhancing urinary bladder carcinogenesis.

Acetaminophen↗
PubMed1984

Promotive effect of primary and secondary bile acids on the induction of gamma-glutamyl transpeptidase-positive liver cell foci as a possible endogenous factor for hepatocarcinogenesis in rats.

The promoting effects of 5 bile acids on liver carcinogenesis were investigated in male Fischer rats initially treated with diethylnitrosamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given bile acids for 8 weeks. At 3 weeks following DEN administration, all rats were subjected to partial hepatectomy. Among the bile acids tested, cholic acid (CA) and deoxycholic acid (DCA) exerted promoting activity as evidenced by significantly increased values of gamma-glutamyl transpeptidase-positive (gamma-GT+) foci as compared with the corresponding controls given DEN alone. In contrast, the other 3 bile acids tested, chenodeoxycholic acid (CDCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA), did not significantly increase the level of gamma-GT+ foci over that induced by DEN alone. It is noteworthy that only bile acids of the same metabolic pathway, CA as a primary bile acid and DCA as a secondary bile acid, showed promoting effects whereas CDCA and its metabolic derivatives, LCA and UDCA, were inactive. The results indicate that CA and DCA might act as endogenous promoters of hepatocarcinogenesis in pathological conditions with increased levels of serum bile acids.

Animals↗
PubMed1984

Modifying potential of thirty-one chemicals on the short-term development of gamma-glutamyl transpeptidase-positive foci in diethylnitrosamine-initiated rat liver.

The modifying potential of 31 different compounds on the development of gamma-glutamyl transpeptidase-positive (gamma-GT+) liver cell lesions was compared in an in vivo short-term assay system. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine intraperitoneally and 2 weeks later were treated with test compounds for 6 weeks and then sacrificed, all rats being subjected to partial hepatectomy at week 3. Modifying potential was scored by comparing the number and area (mm2)/cm2 of induced gamma-GT+ foci with those of the corresponding control group given DEN alone. 2-Acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, phenobarbital, barbital, dipyrone and deoxycholic acid caused a significant enhancement of both the number and area of foci. 4-Acetylaminofluorene, ethionine, benzo[alpha]pyrene, disulfiram and cholic acid had a moderate enhancing effect, whereas slight, but not unequivocal, increases in gamma-GT+ foci were observed after captafol, glutathione, sodium ascorbate and taurine administration. In contrast, acetaminophen, ethoxyquin, butylated hydroxyanisole, butylated hydroxytoluene, and ethyl alcohol showed clear inhibitory effects. It is concluded that the present short-term in vivo system has practical application for the screening of modifying agents for liver tumorigenesis including hepatocarcinogens.

Animals↗
PubMed1984

Promoting activities of butylated hydroxyanisole, butylated hydroxytoluene and sodium L-ascorbate on forestomach and urinary bladder carcinogenesis initiated with methylnitrosourea in F344 male rats.

The promoting effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and sodium L-ascorbate on two-stage carcinogenesis initiated with methylnitrosourea (MNU) in F344 male rats were investigated. Animals were given injections of MNU (20 mg/kg ip) twice a week for 4 weeks, and then basal diet containing 2% BHA, 1% BHT or 5% sodium L-ascorbate for the next 32 weeks. Administration of BHA, BHT or sodium L-ascorbate in the diet significantly increased the incidences per group and numbers per rat of papilloma and papillary or nodular hyperplasia of the urinary bladder, and BHA and BHT also increased the number of cancers per rat. Furthermore BHA significantly increased the incidences of cancer and papilloma in the forestomach of rats initiated with MNU, whereas treatment with BHA alone was associated with papilloma but no carcinoma development in the rat forestomach. The incidence of adenoma, but not adenocarcinoma, of the thyroid was significantly increased by treatment with MNU plus BHT. These results show that BHA, BHT and sodium L-ascorbate have promoting activities on urinary bladder carcinogenesis in rats initiated with MNU, and that BHA also has a promoting effect on forestomach carcinogenesis after initiation with MNU.

Animals↗
PubMed1984

Drugs, food additives and natural products as promoters in rat urinary bladder carcinogenesis.

The promoting effects of various chemicals on urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats were given BBN at 0.01% or 0.05% in their drinking-water for four weeks. One of the following chemicals was then administered in the diet for 32 or 34 weeks: acetazolamide, allopurinol, phenobarbital, phenacetin, ortho-phenylphenol, sodium ortho-phenylphenate, diphenyl, sodium L-ascorbate, butylated hydroxyanisole, butylated hydroxytoluene, sodium saccharin, aspartame, sodium cyclamate, stevioside, DL-tryptophan, quercetin, caffeine, nicotine and hippuric acid. Phenacetin, sodium ortho-phenylphenate, sodium L-ascorbate and butylated hydroxyanisole were significant promoters of urinary bladder neoplasia in rats initiated with BBN. Sodium saccharin, diphenyl, butylated hydroxytoluene, allopurinol, and DL-tryptophan caused moderate or slight promotion of neoplastic changes in the experimental animals. No change in tumour yield was observed after administration of the other chemicals.

Animals↗
PubMed1983

Carcinogenicity and toxicity tests on p-phenylenediamine in F344 rats.

p-Phenylenediamine, an intermediate of oxidative-type hair dyes, was administered to groups of male and female F344 rats in their diet. A subacute toxicity test showed that 0.4% p-phenylenediamine was very toxic to both sexes, but that 0.2, 0.1 and 0.05% p-phenylenediamine induced no remarkable toxic changes in either sex. In a chronic toxicity test 0.1 and 0.05% p-phenylenediamine were given to both sexes in their diet for 80 weeks, but no carcinogenic effects were found in either sex.

Animals↗
PubMed1983

Survey of various chemicals for initiating and promoting activities in a short-term in vivo system based on generation of hyperplastic liver nodules in rats.

The effects of pre- (initiation stage) and post- (promotion stage) administration of 17 chemical carcinogens (including both hepatic and non-hepatic carcinogens), 3 promoters and 2 non-carcinogenic analogs, on the induction of liver hyperplastic nodules were investigated in rats. Test chemicals were administered during the initiation stage after which rats were fed dietary N-2-fluorenylacetamide (2-FAA) for 2 weeks in conjugation with necrogenic CCl4 to enhance production of nodules initiated by test chemicals. Alternatively, effects of test chemicals administered during the promotion phase were evaluated in rats given a combination of dietary 2-FAA for 2 weeks and necrogenic CCl4. This initiation regimen resulted in very few nodules unless a promoter was subsequently used. All chemical carcinogens administered during the initiation stage induced more frequent, larger hyperplastic nodules than did control treatments. However, neither the promoters nor the non-carcinogenic analogs induced hyperplastic nodules if they were administered during the initiation stage. In contrast, hepatocarcinogens and a promoter of hepatocarcinogenesis (phenobarbital) administered in the promotion stage had enhancing (promoting) activity on hyperplastic liver nodules, whereas non-hepatocarcinogens, a promoter for skin carcinogenesis (12-O-tetradecanoylphorbol-13-acetate) and a promoter for urinary bladder carcinogenesis (saccharin) did not. Non-carcinogenic analogs were not active when administered during either the initiation or promotion stages. These findings demonstrated the utility of employing short-term in vivo assays for both initiating and enhancing (promoting) activities of chemicals. By our system, chemicals were classified into 4 main groups, namely, (i) hepatocarcinogens which have both initiating and enhancing activity, (ii) non-hepatocarcinogens with initiating activity only, (iii) promoters of hepatocarcinogenesis which have promoting activity and (iv) non-carcinogens and non liver promoters which did not initiate nor promote nodule development. This is a more discriminating means of assaying carcinogenic activity than is possible with short-term in vitro screening assays for mutagenicity.

Animals↗
PubMed1983

Membrane potentials of urinary bladder epithelium in F344 rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine or sodium saccharin.

Membrane potentials of the urinary bladder epithelium in F344 male rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) or sodium saccharin were measured. In experiment 1, membrane potentials were measured sequentially in the early stage of their change on treatment with 0.05% BBN in the drinking water or with basal diet containing 5% sodium saccharin. Membrane potentials were measured with microelectrodes in weeks 1, 2, 4 and 8 of the experiment. The potential of the group treated with BBN was significantly higher than that of the controls from as early as week 1 until the end of the experiment. In experiment 2, the dose-dependence of the effects of BBN and sodium saccharin on the membrane potential was examined. F344 male rats were treated with 0.05, 0.01, 0.005 or 0.001% BBN in the drinking water, or 5, 1, 0.2 or 0.04% sodium saccharin in basal diet. Clear dose-dependence was observed in the effect of BBN on the potential, but of the doses of sodium saccharin used, only 5% saccharin caused a significantly higher potential than in the control group. These findings suggested that in the early stage of urinary bladder carcinogenesis induced by BBN, the Na+ channel located in the apical membrane may be inactivated.

Animals↗
PubMed1983

Promoting activities of butylated hydroxyanisole and butylated hydroxytoluene on 2-stage urinary bladder carcinogenesis and inhibition of gamma-glutamyl transpeptidase-positive foci development in the liver of rats.

Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) were evaluated for possible promoting activity for urinary bladder carcinogenesis in male F344 rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The rats were treated with 0.01 or 0.05% BBN in the drinking water for 4 weeks and then administered 2% BHA or 1% BHT in the diet for 32 weeks. Surviving rats were killed at the end of week 36 of the experiment. The incidences of cancer and papilloma and the average number of cancers, papillomas and papillary or nodular hyperplasias (PN hyperplasias) per 10 cm of basement membrane were significantly increased in the group receiving BHA following initiation by 0.05% BBN compared with the group given BBN only. BHT also significantly increased these lesions of the bladder, but not the average number of cancers, in rats treated with 0.05% BBN. The ability of four antioxidants, BHA, BHT, sodium L-ascorbate (ascorbate) and ethoxyquin, to promote the induction of gamma-glutamyltranspeptidase (gamma-GT)-positive foci initiated by diethylnitrosamine (DENA) in the liver of F344 rats was tested. Rats were given a single i.p. injection of 200 mg/kg body weight of DENA, and 2 weeks later the animals were exposed to 2% BHA, 1% BHT, 5% ascorbate or 1% ethoxyquin, respectively, in the diet for 6 weeks. All animals were subjected to partial hepatectomy at the end of week 3. The number of gamma-GT-positive foci in the groups fed either BHA, BHT or ethoxyquin after DENA were significantly decreased compared with the control group. These findings show that BHA and BHT are promoters for the urinary bladder carcinogenesis initiated by BBN, but that these and other antioxidants significantly inhibit the induction of gamma-GT-positive foci in the liver.

Acyltransferases↗
PubMed1983

Modifying factors in urinary bladder carcinogenesis.

N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is a potent carcinogen in the urinary bladder of animals. The BBN model of bladder cancer is an excellent model of human urinary bladder cancer and has already led to a greater knowledge of its pathogenesis. In our studies, histogenesis and morphological characteristics of BBN urinary bladder cancer were analyzed in different animal species such as rats, mice, hamsters and guinea pigs and also in different rat strains. Papillary or nodular hyperplasia (PN hyperplasia) is found to be a preneoplastic lesion of the rat urinary bladder. Therefore, the promoting and inhibitory effects of various chemicals in two-stage urinary bladder carcinogenesis were judged by measuring PN hyperplasia in rats. Dose-dependent and organ-specific effects of the urinary bladder promoter, saccharin, in the induction of PN hyperplasia were shown in rats after initiation by BBN. The promoting effect of saccharin was seen more clearly in the urinary bladder of rats after potent initiation. A strain difference in susceptibility of the urinary bladder to the promoter was also shown. These results suggest that the above various factors may also have modifying activities on urinary bladder carcinogenesis in man.

Animals↗
PubMed1983

Comparison of the promoting effects of various agents in induction of preneoplastic lesions in rat liver.

The promoting activities of 29 compounds on induction of hyperplastic (neoplastic) liver nodules (HN) and the dose-dependent effects of tumor promoting agents were compared by using a short-term test system developed in this laboratory. In tests on promoting activity, F344 rats were given a single dose (200 mg/kg) of N-nitrosodiethylamine (DEN), and from two weeks later, were treated with various test compounds for 6 or 10 weeks. They were subjected to partial hepatectomy 3 or 4 weeks after DEN treatment. The results showed that strong hepatocarcinogens, such as aflatoxin B1, DEN, N-nitrosodimethylamine (DMN), 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and ethionine, induced many hyperplastic liver nodules, whereas dieldrin, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), polychlorinated biphenyls (PCB) and alpha-hexachlorocyclohexane (alpha-HCH) induced few lesions. Nonhepatocarcinogens, such as N-nitrosoethylurea (ENU) and 3-methylcholanthrene (3-MC), only slightly induced hyperplastic nodules. Of the miscellaneous compounds tested, phenobarbital, deoxycholic acid and ethynyl estradiol also induced gamma-glutamyl transpeptidase (gamma-GT) positive foci. In tests on the dose-dependent effects of promoting agents, DMN was given at different concentrations for 6 weeks from 2 weeks after DEN treatment. Results were quantitated by histochemical measurement of the number or area of gamma-GT positive lesions induced. A long-term experiment on the effect of feeding DMN for 96 weeks was also done. Clear dose-dependent effects of DMN were seen in induction of gamma-GT positive foci in the short-term experiment and neoplastic lesions in the long-term one.

2-Acetylaminofluorene↗
PubMed1983

Membrane potential of rat urinary bladder epithelial cells.

Rat urinary bladder epithelial cells exhibited a membrane potential of about -22 (apical) and -24 (basal) mV in normal Krebs solution. Blockade of Na+ entry through the apical membrane by Na+ depletion of administration of amiloride, or inactivation of the Na pump in the basal membrane by ouabain resulted in marked hyperpolarization of the epithelial cells. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), a specific carcinogen, and saccharin, a potent enhancer of carcinogenesis, inhibited development of the Na+ channel and/or Na pump on the bladder epithelium. This physiology may contribute to the abnormal intracellular environment leading to bladder carcinoma.

Animals↗