phenylephrine-hydrochloride and Liver-Neoplasms

The carcinogenicity and chronic toxicity of hydrazine monohydrate was examined by administrating hydrazine monohydrate in drinking water to groups of 50 F344/DuCrj rats and 50 Crj:BDF1 mice of both sexes for two years. The drinking water concentration of hydrazine monohydrate was 0, 20, 40 or 80 ppm (wt/wt) for male and female rats and male mice; and 0, 40, 80 or 160 ppm for female mice. Survival rates of each group of males and females rats and mice were similar to the respective controls, except female rats administered 80 ppm. Two-year administration of hydrazine monohydrate produced an increase in the incidences of hepatocellular adenomas and carcinomas in rats of both sexes along with hepatic foci. In mice, the incidences of hepatocellular adenomas and carcinomas were increased in females, and significantly increased incidences of hepatocellular adenomas in females administered 160 ppm were observed. Thus, hydrazine monohydrate is carcinogenic in two species, rats and mice. Additionally, non-neoplastic renal lesions in rats and mice and non-neoplastic nasal lesions in mice were observed.

Topics: Adenoma; Administration, Oral; Animals; Biomarkers; Body Weight; Carcinogenicity Tests; Carcinogens; Carcinoma; Cell Transformation, Neoplastic; Drinking; Drinking Water; Eating; Female; Hydrazines; Kidney; Liver Neoplasms; Male; Mice; Nose; Rats, Inbred F344; Risk Assessment; Sex Factors; Species Specificity; Time Factors; Toxicity Tests, Chronic

Beta-myrcene, an acyclic unsubstituted monoterpene, and the essential oils which contain it are used as intermediates in the production of terpene alcohols (geraniol, nerol, and linalool), which, in turn, serve as intermediates in the production of aroma and flavor chemicals. Thus beta-myrcene is used widely in cosmetics, soaps, and detergents and as a flavoring additive in food and beverages. Beta-myrcene is also the major constituent of hop and bay oils, which are used in the manufacture of alcoholic beverages. Beta-myrcene was nominated for study by the National Institute of Environmental Health Sciences based on its high production volume, high level of human exposure, and structural relationship to d-limonene, which induced neoplasms in the kidneys of male rats in association with hyaline droplet nephropathy (NTP, 1990). Male and female F344/N rats and B6C3F1 mice were administered beta-myrcene (greater than 90% pure) by gavage for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 0.25, 0.5, 1, 2, or 4 g beta-myrcene/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. Additional groups of 10 male and 10 female special study rats were administered the same doses for 23 days. All core study rats in the 4 g/kg groups died during the first week of the study except one male that died on day 11. One to three rats in the 1 and 2 g/kg groups and one 0.5 g/kg male died by week 10 of the study. One 2 g/kg female died during the last week of the study. Except for lesion incidence data in groups administered 2 g/kg or less, data from rats that died early were excluded from the analysis and summary tables. Mean body weights were significantly decreased in male rats in the 0.5, 1, and 2 g/kg groups. Special study rats in the 4 g/kg groups died by the end of the first week. Dose-related clinical findings in animals that died early included thinness, lethargy, abnormal breathing, and ruffled fur. Right kidney and liver weights of dosed males and females were generally significantly greater than those of the vehicle controls. In special study rats evaluated on day 23, the incidences and severities of chronic progressive nephropathy (CPN) and renal tubule degeneration were increased in 2 g/kg males. At the end of the 3-month study, the incidences of renal tubule necrosis were. beta-myrcene did not show evidence of genotoxicity in assays conducted by the NTP. No mutagenicity was observed in any of several strains of Salmonella typhimurium or Escherichia coli in two independent Ames assays conducted with and without exogenous metabolic activation. In addition, no significant increase in frequency of micronucleated normochromatic erythrocytes, biomarkers of chromosomal damage, was observed in male or female mice administered beta-myrcene for 3 months by gavage.. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of beta-myrcene in male F344/N rats based on increased incidences of renal tubule neoplasms. There was equivocal evidence of carcinogenic activity of beta-myrcene in female F344/N rats based on increased incidences of renal tubule adenoma. There was clear evidence of carcinogenic activity of beta-myrcene in male B6C3F1 mice based on increased incidences of hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma. There was equivocal evidence of carcinogenic activity of beta-myrcene in female B6C3F1 mice based on marginally increased incidences of hepatocellular adenoma and carcinoma. Administration of beta-myrcene induced nonneoplastic lesions in the kidney of male and female rats, nose of male rats, and liver of male and female mice. Synonyms: 2-Methyl-6-methylene-2,7-octadiene; 7-methyl-3-methylene-1,6-octadiene; myrcene.

Topics: Acyclic Monoterpenes; Adenoma; Animals; Carcinogenicity Tests; Carcinoma, Hepatocellular; Female; Hepatoblastoma; Humans; Kidney; Kidney Neoplasms; Liver Neoplasms; Longevity; Male; Mice; Mice, Inbred Strains; Monoterpenes; Mutagenicity Tests; Neoplasms, Experimental; Nose; Rats; Rats, Inbred F344; Toxicity Tests, Chronic

We report on a boy with proximal interstitial deletion of chromosome 4, del(4)(q21.22q23). The patient was born at term with a low birth weight, flat nasal bridge, micrognathia, wide-spaced nipples, clinodactyly of fifth fingers, overlapping fingers, post-axial polydactyly of the right foot, micropenis, hypospadias, a dermal sinus, and cardiac malformations. He developed psychomotor retardation, seizures, and a liver tumor with an increased serum alpha-fetoprotein level and rapid growth. The patient carried a deletion of chromosome 4 involving the 4q21-q22 region that was reported to form a unique syndrome. The absence of central nervous system overgrowth and the presence of a malignant liver tumor are unique to our patient, compared to others with the 4q21-q22 deletion syndrome. The clinical manifestations and relationship between the liver tumor and chromosomal anomaly are discussed.

Topics: Abnormalities, Multiple; Birth Weight; Chromosome Deletion; Chromosomes, Human, Pair 4; Heart Defects, Congenital; Humans; Hypospadias; Infant; Japan; Karyotyping; Liver Neoplasms; Male; Nose; Penis; Polydactyly; Psychomotor Performance

Hemangiopericytomas, rare perivascular tumors, normally tend to be well circumscribed, however, since some have a malignant behavior they are recognized to be potentially malignant.. In the case presented here, we report the medical history of a 46-year-old man with a hemangiopericytoma of the nose. In 1983, the tumor was surgically removed, and histological examination revealed no signs of malignancy. In 1987, a local recurrence was removed followed by X-irradiation. In March 1995, the patient presented with multiple hepatic and bone metastases. Chemotherapy with ifosfamide (5 g/m2, day 1) and epirubicin (50 mg/m2, day 1) was performed. After three courses of chemotherapy a tumor stabilization was achieved. In November 1995, however, a massive progression of the hepatic lesions was found. Therefore, six courses of a second-line chemotherapy with dacarbazine (200 mg/m2, day 1 to 5) and adriamycin (60 mg/m2, day 1) were applied. A partial remission was achieved lasting until November 1996. A couple of weeks later the patient died due to hepatic failure.. Despite of unacceptably low survival rates in patients with advanced soft tissue sarcomas (especially after pretreatment with ionizing radiation) our report demonstrates that it is also possible to induce long lasting remissions without altered quality of life.

Topics: Combined Modality Therapy; Fatal Outcome; Follow-Up Studies; Hemangiopericytoma; Humans; Liver; Liver Neoplasms; Male; Middle Aged; Nose; Nose Neoplasms; Salvage Therapy

The purpose of this study was to determine the frequency of immunoglobulin deposition in the haired skin, footpads, and nasal planums of 10 WHV-infected woodchucks with chronic hepatitis and hepatocellular carcinoma and compare these results with those reported in humans. Immunoglobulin deposition was detected in the skin samples of 3 of 10 woodchucks. Granular deposits were revealed in the superficial dermal blood vessels of the nasal planum, lateral thoracic skin, and footpads in 1 animal each. In 1 of these animals, (lateral thorax) immunoglobulin deposition was concurrently present at the basement membrane zone.

Topics: Animals; Biopsy, Needle; Carcinoma, Hepatocellular; Chronic Disease; Disease Models, Animal; Female; Fluorescent Antibody Technique; Foot; Hair; Hepadnaviridae; Hepatitis, Viral, Animal; Immunoglobulins; Liver Neoplasms; Male; Marmota; Nose; Skin

Topics: Animals; Carcinogens; Cricetinae; Female; Liver; Liver Neoplasms; Male; Nitrosamines; Nose; Nose Neoplasms; Trachea; Tracheal Neoplasms

Topics: Granuloma; Granuloma, Lethal Midline; Humans; Liver Neoplasms; Mesenchymoma; Nose