Stomach carcinogenicity of caffeic acid, sesamol and catechol in rats and mice.

The carcinogenic potential of caffeic acid, sesamol and catechol was examined in male and female F344 rats and B6C3F1 mice, groups of 30 animals being treated with diets containing 2% caffeic acid, 2% sesamol or 0.8% catechol for 104 weeks (rats) or 96 weeks (mice). Histological examination revealed that caffeic acid induced forestomach squamous cell carcinoma in 57% (P less than 0.

Enhancing effect of oxymetholone, an anabolic steroid, on development of liver cell foci in rats initiated with N-diethylnitrosamine.

The promoting potential of oxymetholone (OXM) administration on development of liver cell foci was investigated in male F344 rats previously treated with N-diethylnitrosamine (DEN). One week after a single injection of DEN (100 mg/kg, i.p.

Formation of 8-hydroxydeoxyguanosine (8-OH-dG) in rat kidney DNA after intraperitoneal administration of ferric nitrilotriacetate (Fe-NTA).

A significant increase of 8-hydroxydeoxyguanosine (8-OH-dG) was observed in the kidney DNA of rats given a renal carcinogen, the ferric complex of nitrilotriacetate (Fe-NTA) by single i.p. injection.

Regression of butylated hydroxyanisole (BHA)-induced hyperplasia but not dysplasia in the forestomach of hamsters.

The reversibility of butylated hydroxyanisole (BHA)-induced hamster forestomach hyperplasia was examined histopathologically. Groups of 10-15 male Syrian golden hamsters were treated with 2% BHA, for 12, 24 or 48 weeks and in each case then placed on basal diet until termination of the experiment at week 72, or treated with 2% BHA continuously for 72 weeks. Although sequential sampling revealed that BHA-induced hyperplasia reverted after cessation of antioxidant treatment, dysplastic lesions such as squamous cell dysplasia and basal cell dysplasia persisted and tended to increase with time on BHA.

Bladder epithelial hyperplasia in F344 rats after intravesical instillation of the antitumor chemotherapeutic agents Adriamycin and mitomycin C.

The effects of intravesical instillation of the antineoplastic antibiotics, Adriamycin or mitomycin C, on the urinary bladder epithelium of female F344 rats were evaluated using a combined immunohistochemical and morphological approach. Four weeks treatment with Adriamycin or mitomycin C induced an increase of DNA synthesis and was associated with simple hyperplasia characterized by elevated nuclear cytoplasmic ratios, cytomegaly and pleomorphism. Under the scanning electron microscope (SEM), luminal cell surface alterations such as pleomorphic microvilli were observed.

Acute toxicity tests on 113 environmental chemicals.

Acute toxicity tests on 113 environmental chemicals were conducted by the order of the Japanese government agencies. the LD50s or LC50s for 23 household chemicals, 11 medical drugs, 10 drug additives, 20 food additives, 13 industrial chemicals, 14 environmental pollutants, 12 agricultural chemicals and 5 organic solvents are presented together with the major toxic signs and symptoms and macroscopic changes in tissues. These toxicity data will be useful as an information source for regulatory purposes and also for prediction of the potential for acute toxicity of a wide variety of new chemicals.

Modification by catechol and resorcinol of upper digestive tract carcinogenesis in rats treated with methyl-N-amylnitrosamine.

Modifying effects of the environmental contaminant catechol, and its isomers resorcinol and hydroquinone, on methyl-N-amylnitrosamine (MNAN)-induced carcinogenesis were studied in male F344 rats. Groups of 15 rats were given three i.p.

Correlation between the DNA damage in urinary bladder epithelium and the urinary 2-phenyl-1,4-benzoquinone levels from F344 rats fed sodium o-phenylphenate in the diet.

The relationship between urinary metabolites and DNA damage in the urinary bladder epithelium of male and female rats was tested by alkaline elution assay after an intravesical injection of OPP or its urinary metabolites. 2-Phenyl-1,4-benzoquinone (PBQ) revealed a weak DNA-damaging activity in both sexes at 0.05-0.

Synergistic effects of low-dose hepatocarcinogens in induction of glutathione S-transferase P-positive foci in the rat liver.

The effects of combined administration of hepatocarcinogens at low doses on the development of glutathione S-transferase P-form (GST-P)-positive foci of rat liver were examined utilizing a bioassay model which consists of a single injection of diethylnitrosamine (DEN, 200 mg/kg, ip), two-thirds partial hepatectomy at week 3 and a 6-week administration of test compounds. The chemicals used, 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), phenobarbital (PB), thioacetamide (TAA), N-ethyl-N-hydroxyethylnitrosamine (EHEN), benzo[a]pyrene (B[a]P), carbazole, and alpha-hexachlorocyclohexane (alpha-HCH) were incorporated in the diet, except for EHEN which was dissolved in the drinking water, at levels of 1/6 of the doses usually used. The combinations were: I) 2-AAF, 3'-Me-DAB, PB, TAA, EHEN and B[a]P, II) 2-AAF, 3'-Me-DAB and PB, III) TAA, EHEN and B[a]P, IV) 2-AAF, 3'-Me-DAB, carbazole, TAA, EHEN and alpha-HCH, V) 2-AAF, 3'-Me-DAB and carbazole, and VI) TAA, EHEN and alpha-HCH.

Promotion by dihydroxybenzene derivatives of N-methyl-N'-nitro-N-nitrosoguanidine-induced F344 rat forestomach and glandular stomach carcinogenesis.

Modifying effects of resorcinol, hydroquinone, p-tert-butylcatechol (PTBC), p-methylcatechol (PMC), and o-methylcatechol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced forestomach and glandular stomach carcinogenesis were investigated in F344 rats. Groups of 15 to 16 male 6-wk-old animals were given a single intragastric administration of 150 mg/kg of body weight of MNNG and starting 1 wk later were administered powdered diet containing 0.8% resorcinol, 0.

In situ freezing of the rat urinary bladder: DNA adduct formation in the bladder epithelium demonstrated by 32P-postlabeling assay.

In situ freezing of the urinary bladder has been demonstrated to exert tumor-initiating potential in two-stage urinary bladder carcinogenesis in the rat. In the present experiment, DNA modification was examined after in situ freezing of the whole urinary bladder performed by pinching with frozen forceps at -15 degrees C or -30 degrees C for 2 s. The 32P-postlabeling analysis revealed at least 2 DNA adducts in the epithelial cells of the urinary bladder collected 3 days after freezing.

Sodium o-phenylphenate (OPP-Na) promotes skin carcinogenesis in CD-1 female mice initiated with 7,12-dimethylbenz[a]anthracene.

Sodium o-phenylphenate (OPP-Na) was applied at a dose level of 5.0 mg/animal dermally to the fur-clipped dorsal area of female CD-1 mice twice weekly for 47 weeks after applications of 10 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator twice weekly for 5 weeks. A total of 25 skin tumors (21 papillomas and four carcinomas) developed in 15 out of 20 mice (75%).

Effects of nisoldipine on sympathetic activity, the renin-angiotensin-aldosterone system, and water-sodium-calcium metabolism in patients with essential hypertension.

The effects of nisoldipine (Bay k 5552), a long-acting Ca2+ antagonist, on sympathetic activity, the renin-angiotensin-aldosterone (RAA) system, the renal metabolism of water and electrolytes, and parathyroid hormone (PTH) were investigated following single dose and 4 weeks administration. The administration of nisoldipine led to the following results: 1. Mean arterial pressure (MAP) fell and heart rate slightly increased after the first dose, but did not show any appreciable change over 4 weeks treatment.

Teratoma of the spinal cord. A case report with CT scans.

Teratomas in the spinal cord are rare. We report a case in a 54-year-old man. CT scans revealed tumours of different densities within the spinal canal; this heterogeneity may help to differentiate teratoma from other spinal cord tumours.

Sequential analysis of quinoline-induced hepatic hemangioendothelioma development in rats.

The effect of duration of quinoline treatment on the induction of hepatic hemangioendotheliomas was examined. Groups of male Wistar rats were given 0.25% quinoline in the diet for 4, 8, 12, 16 or 20 weeks and sequentially killed at these time points.

In situ freezing of the urinary bladder: a trigger of rapid development of sodium o-phenylphenate-induced urinary bladder tumors in the rat.

The effect of in situ freezing of the urinary bladder on sodium o-phenylphenate (OPP-Na)-induced urinary bladder tumor development was investigated in male F344 rats. Freezing was performed at the start of the experiment by touching the serosal surface of the bladder with a frozen steel rod. As a result, three out of 27 rats (11%) developed bladder tumors within 78 weeks when 0.

Effect of aspirin on urinary bladder carcinogenesis initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in rats.

N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT), a potent urinary bladder carcinogen, is metabolically activated in vitro by a variety of enzyme systems including aerobic cooxidation by prostaglandin H synthase which is present in the rat bladder mucosa. In a previous experiment, aspirin coadministered with FANFT for 12 weeks inhibited FANFT-induced bladder carcinogenesis and enhanced forestomach carcinogenesis. To further evaluate the effects of aspirin on FANFT carcinogenesis, male F344 rats were fed either FANFT (0.

Long-term feeding study of N,N'-diphenyl-p-phenylenediamine in F344 rats.

Groups of 50 F344 rats of each sex were fed a diet containing 0.5 or 2% of N,N'-diphenyl-p-phenylenediamine (DPPD) for 104 weeks and were killed 8 weeks after the cessation of DPPD administration. DPPD-treated rats of both sexes showed a dose-dependent reduction in body weight gain, but no lower survival rate, when compared with untreated control rats.

Bladder cancers. Their process of development and its modification.

Much information on the development of bladder cancers and its modification has accumulated. It is generally considered that the presence of chemicals in the environment including carcinogens and modifiers (promoters, inhibitors, anti-promoters, etc.) is responsible for the geographical variation in human neoplasia including urinary bladder cancer development.

Rapid bioassay methods for carcinogens and modifiers of hepatocarcinogenesis.

It is very important to detect environmental carcinogens in a short period. For this purpose, a rapid bioassay system based on two-step hepatocarcinogenesis has been developed in our laboratory. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.

[Collaborative study of Japanese Pharmacopoeia Heparin Sodium Reference Standard (Control 871)].

Heparin Sodium Reference Standard for Japanese Pharmacopoeia (JP) is replaced with new material derived from porcine mucosa. The material was dissolved in water, distributed to vials and freeze-dried. The anticoagulant activity of the freeze-dried product was determined in collaboration with four laboratories employing JP method.

Medium-term bioassay system for detection of carcinogens and modifiers of hepatocarcinogenesis utilizing the GST-P positive liver cell focus as an endpoint marker.

We have developed a medium-term bioassay system of 8 weeks duration utilizing male Fischer 344 (F344) rats for detection of liver carcinogens and modifiers of hepatocarcinogenesis. The system consists of a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg), 6-weeks-administration of test chemical beginning 2 weeks after the DEN injection, and 2/3 partial hepatectomy (PH) performed at week 3. Carcinogenic potency of test chemicals is predicted based on the results of quantitative analyses of immunohistochemically-demonstrated glutathione S-transferase placental form (GST-P) positive liver cell foci.

Carcinogenicity study of tetramethylthiuram disulfide (thiram) in F344 rats.

The carcinogenic potential of tetramethylthiuram disulfide (thiram) was examined in F344 rats. Groups of 50 male and 50 female rats were given thiram in their diet at concentrations of 0.1% and 0.