Use of topical ivermectin treatment for Syphacia obvelata in mice.
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Administration, Topical↗
Biomedical subjects
C A Montgomery
Publications and source records attributed to C A Montgomery.
Diagnostic exercise: skin infarction in rats.
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Animals↗
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.
Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
Alleles↗
Cultured breast cystosarcoma phylloides cells and applications to patient therapy.
Malignant cystosarcoma phylloides (CP) is a relatively rare cancer of the breast. A CP tumor was processed as part of a tumor acquisition, propagation, and preservation program in patient biotherapy. Two tissue culture cell lines were developed from this tumor, one directly from the biopsy, another from a xenograft tumor grown in athymic mice. The two cell lines were similar in character. There was strong immunochemical reactivity with antibodies to vimentin, type I collagen, and type III collagen. There was no reactivity with antibodies to cytokeratin and epithelial membrane antigen. Both cell lines were aneuploid, clonogenic in soft agar, and tumorigenic in nude mice. 5 alpha-dihydrotestosterone and thyroxine added to the culture medium stimulated growth, while testosterone, 17 beta-estradiol, and 4-hydroxytamoxifen were without effect. Dexamethasone and cortisol were inhibitory at high doses (10(-6) M). Dibutyryl cyclic AMP, theophylline, and vitamin C were all inhibitory. The biopsy contained tumor-infiltrating lymphocytes which proliferated in cultures containing interleukin 2. The expanded lymphocytes were activated T cells which had the capacity to lyse tumor cells. These results suggest possibilities in the therapy of cystosarcoma phylloides involving vitamin C, certain hormones, and tumor-infiltrating lymphocytes.
Adult↗
Toxicity studies of intravenous vitamin E in newborn rabbits.
This study was designed to investigate the toxicity of intravenously administered alpha-tocopherol, alpha-tocopheryl acetate, and a polysorbate vehicle similar to that used in a commercial preparation of alpha-tocopheryl acetate intended for intravenous administration. Cesarean-delivered newborn rabbits fed intravenously were administered 100 mg of either alpha-tocopherol or alpha-tocopheryl acetate in a polysorbate vehicle, or the vehicle only, or no treatment for 6 or 7 days. Two intravenous diets were employed which differed in nutritional content and were termed low energy (LE) and high energy (HE). High concentrations of alpha-tocopherol were present in the tissues of all pups that received either treatment with alpha-tocopherol or alpha-tocopheryl acetate in the polysorbate vehicle, irrespective of the nutritional regimen. Pups in all treatment and control groups which received the LE diet had hepatic centrilobular degeneration, necrosis and pigment accumulation, which was attributed to malnutrition. No additional toxicities could be attributed to the vitamin E or polysorbate treatments. Administration of the HE diet eliminated the nutrition-related centrilobular degeneration, and revealed treatment-related liver changes. HE pups treated with alpha-tocopheryl acetate in the polysorbate vehicle had microscopic evidence of mild bile stasis and had elevated serum bilirubin. Minimal lipidosis or fatty change in the liver was observed only in alpha-tocopherol and alpha-tocopheryl acetate-treated pups. Lipidosis in the spleen was moderate in the alpha-tocopherol group and minimal in the alpha-tocopheryl acetate group. Lipidosis also occurred in the adrenal gland primarily in the alpha-tocopheryl acetate group.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Kidney and urinary bladder lesions in F344/N rats and B6C3F1 mice after 13 weeks of 2,2-bis(bromomethyl)-1,3-propanediol administration.
Thirteen-week toxicity studies of the flame retardant 2,2-bis(bromomethyl)-1,3-propanediol (BMP; dibromoneopentyl glycol; FR-1138; CAS No. 329690-0) were conducted in male and female F344/N rats and B6C3F1 mice. The chemical was administered by oral gavage in corn oil 5 days per week for 13 weeks to rats at doses of 0, 50, 100, 200, 400, and 800 mg/kg and to mice at doses of 0, 25, 50, 100, 200, and 400 mg/kg, or in the feed for 13 weeks at concentrations of 0, 1250, 2500, 5000, 10,000, and 20,000 ppm for rats and at 0, 625, 1250, 2500, 5000, and 10,000 ppm for mice. There was a dose-related decrease in body weight gain in rats and mice after chemical administration. Mortality attributed to toxicity of BMP was seen in the gavage study in 2/10 high-dose (800 mg/kg) male rats and 3/10 high-dose (400 mg/kg) male mice no dose-related mortality occurred in the feed study. Minimal degeneration in the renal papilla was seen in male rats at 800 mg/kg in the gavage study and at doses of 5000 ppm or more in the feed study. This was also present in one female rat at the 20,000 ppm dose. In male mice renal papillary necrosis occurred at 400 mg/kg after dosing by the gavage route and at 2500, 5000, and 10,000 ppm in the dosed-feed study. In female mice papillary necrosis occurred only at the 10,000 ppm dose in the feed study. Tubular cell regeneration of the renal cortex was also present in mice at the same dose levels at which the papillary necrosis was observed. Transitional cell hypeplasia of the urinary bladder was seen in male rats at 400 and 800 mg/kg and in both sexes of mice at 200 and 400 mg/kg. Hyperplasia of the urinary bladder was also seen when BMP was administered in the feed at doses of 20,000 ppm to male rats; at doses of 2500, 5000, and 10,000 ppm to male mice; and at doses of 5000 and 10,000 ppm to female mice. The kidney and urinary bladder are target organs when BMP is administered by gavage or the dosed-feed route; mice were more sensitive than rats for the development of kidney and bladder lesions. Male rats and mice were more sensitive than females for the development of renal papillary degeneration or necrosis.
Animals↗
Toxic responses in F344 rats and B6C3F1 mice given roxarsone in their diets for up to 13 weeks.
Thirteen-week toxicity studies were conducted in groups of 10 F344 rats and B6C3F1 mice of each sex fed roxarsone at 0, 50, 100, 200, 400, or 800 ppm in the diet. Arsenic levels in blood, urine, kidneys, and liver of rats were measured in additional animals of each sex dosed with 100 or 400 ppm roxarsone. Compound-related mortality occurred in both sexes of rats at 800 ppm and mice at 800 and 400 ppm. Significant body weight gain depression occurred in both sexes of rats at 200, 400, and 800 ppm and mice at 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats and mice at 800 ppm. Lesions associated with roxarsone administration were noted only in the kidney of rats and were characterized by tubular necrosis and mineralization at the corticomedullary junction. Arsenic levels in urine, blood, liver, and kidneys increased over time and were directly proportional to the level of roxarsone in feed. These levels were greater than 6 times higher in rats than in mice and were about 2 time higher in males than in females. The no-observable-effect level for roxarsone toxicity was estimated at 100 ppm for rats and 200 ppm for mice. No hematology or clinical chemistry effects were found in rats or mice of either sex.
Animals↗
Modulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in F344 rats by di(2-ethylhexyl)phthalate.
The effects of cotreatment with a hyperlipidemic chemical, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and a hypolipidemic agent, di(2-ethylhexyl)-phthalate (DEHP), on lipid metabolism and toxicologic responses were studied in F344 rats. Treatment with TCDD alone (160 micrograms/kg) caused an increase in serum triglycerides and cholesterol while treatment with DEHP alone (2 g/kg/day) caused a decrease in triglycerides and cholesterol versus untreated controls. When administered before or after TCDD, DEHP caused a decrease in TCDD-induced hyperlipidemia. This change was attributed to enhanced hepatic peroxisomal beta-oxidation and decreased hepatic lipid synthesis resulting from treatment with DEHP. TCDD treatment produced a fatty liver, as determined by gravimetric analysis of extracted lipid and microscopic examination of liver sections which revealed extensive cytoplasmic vacuolization that stained positive with Oil Red 0, but did not induce peroxisomal beta-oxidation. Thus, an increase in hepatic or serum lipid levels is not sufficient for induction of peroxisome proliferation. Neither TCDD nor DEHP treatment affected mitochondrial beta-oxidation. Pretreatment of rats with DEHP, followed by daily exposure to this hypolipidemic agent after treatment with TCDD, had a partial protective effect against TCDD-induced fatty liver, body weight loss and mortality. Microscopic examination of liver sections confirmed the suppression of TCDD-induced fatty liver by pretreatment with DEHP. When DEHP treatment was initiated after the TCDD dose, there was less protection against the above parameters of TCDD toxicity. This study demonstrates that TCDD-induced fatty liver, hyperlipidemia and mortality can be antagonized by treatment with a hypolipidemic agent such as DEHP.
Acyl-CoA Oxidase↗
Control of animal pain and distress in cancer and toxicologic research.
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Animal Welfare↗
Comparative toxicity and carcinogenicity of two chlorinated paraffins in F344/N rats and B6C3F1 mice.
The toxicity and carcinogenicity of chlorinated paraffins containing C12 with 60% Cl, and C23 with 43% Cl, were assessed in prechronic and 2-year gavage studies using F344/N rats and B6C3F1 mice of both sexes. Single administrations of chlorinated paraffins were nonlethal in rats and mice, but repeated-dose and 2-year studies demonstrated toxic responses that differed with the paraffins. The C23,Cl43% paraffin produced a granulomatous inflammation in the liver of female rats in 13-week studies, while the C12,Cl60% paraffin caused deaths of rats and mice in 16-day studies and marked liver enlargement in 13-week studies. In 2-year studies, the C23,Cl43% paraffin caused hepatic and lymphatic granulomatous inflammation and hyperplasia in both sexes of rats, and was associated with marginal increases in adrenal medullary pheochromocytomas in female rats and hepatocellular neoplasms in female mice and with clear increases in malignant lymphomas in male mice. The C12,Cl60% paraffin caused marked liver enlargement in rats and increased the severity of nephropathy in male rats and the incidence of nephropathy in female rats. C12,Cl60% also caused hepatocellular neoplasms in both sexes of rats and mice: kidney tubular cell adenomas and adenocarcinomas in male rats, thyroid follicular cell neoplasms in female rats and female mice, and a marginal increase in mononuclear cell leukemia in male rats. Thus, the short-chain, heavily chlorinated paraffin appears to have a greater potential for chronic toxicity and carcinogenicity than the longer-chain, lightly chlorinated paraffin. Both paraffins have been reported to be nonmutagenic in bacteria. (National Toxicology Program (1986) Technical Report, NIH Publications 86-2561 and 86-2564).
Animals↗
Subchronic toxicity of propantheline bromide administered in the feed to Fischer 344/N rats and B6C3F1 mice.
Propantheline bromide, a drug used for the treatment of peptic ulcers, was studied in male and female Fischer 344/N rats and B6C3F1 mice for subchronic toxicity. The drug was administered in the feed for 13 weeks at 0, 220, 670, 2000, 6000, and 24,000 ppm in both species. Propantheline bromide caused a decrease in weight gain at 24,000 ppm in male and female rats and at 6000 and 24,000 ppm in male and female mice. All rats survived the treatment. The top dose of 24,000 ppm was fatal to mice. Clinical signs of toxicity (dilated pupils and decreased gastrointestinal emptying), similar to the atropine-like effects of propantheline bromide in man, were seen in male and female rats at 24,000 ppm. Hyperplasia of the transitional epithelium of the urinary bladder was seen in high-dose male rats at the end of 13 weeks.
Administration, Oral↗
Ovarian choriocarcinoma in the mouse.
Choriocarcinoma is one of the rarest ovarian tumors in any animal species. This paper describes the gross and microscopic appearance of seven such neoplasms in B6C3F1 mice. Mean age at death was 47 weeks. Tumors were described at necropsy as dark or hemorrhagic cystic lesions. On microscopic examination tumors were composed of hematocysts, intercellular hemorrhage, and cytotrophoblasts, syncytiotrophoblasts, and/or trophoblastic giant cells. Cytotrophoblasts, syncytiotrophoblasts, and occasional giant cells were present in three cases while the other four tumors contained only trophoblastic giant cells.
Animals↗
Nonneoplastic lesions of the ovary in Fischer 344 rats and B6C3F1 mice.
The National Toxicology Program's pathology database on 2-year carcinogenicity studies was reviewed for nonneoplastic ovarian disease. Ovaries from 39,941 female Fischer rats and 41,444 female B6C3F1 mice were examined. A variety of inflammatory, degenerative, vascular, and proliferative lesions were documented and are described. The most common ovarian lesions in rats were cysts (6%). The most frequent ovarian lesions in mice were cysts (15%), acute inflammation (4%), degeneration (4%), vascular disease (2.5%), and atrophy (2%). There was no difference in incidence of ovarian disease between controls and treated animals. The frequency of ovarian disease in mice exceeded the frequency in rats in every category.
Animals↗
National Toxicology Program nomenclature for hepatoproliferative lesions of rats.
Diagnostic criteria for hepatoproliferative lesions of Fischer 344 rats are presented to permit more complete categorization of the spectrum of lesions observed in two-year chemical carcinogenicity studies. A nomenclature recently adopted by the National Toxicology Program differs from previous classification schemes in that hepatocellular hyperplasia and hepatocellular adenoma are to be used for lesions which were previously combined under the diagnosis of neoplastic nodule. The term hyperplasia is reserved for proliferative lesions that are perceived to be secondary, nonneoplastic responses to degenerative changes in the liver. Foci of cellular alteration, hepatocellular adenoma, and hepatocellular carcinoma are believed to represent a spectrum of changes that comprise the natural history of neoplasia. This change in nomenclature was made subsequent to a peer review of representative hepatoproliferative lesions from two-year carcinogenicity studies. The revised nomenclature is consistent with traditional pathologic diagnoses for proliferative lesions in other epithelial tissues and should facilitate the interpretation of conventional toxicity and carcinogenicity studies in rats. Morphologic features of other selected rat liver lesions are also presented.
Animals↗
Toxicity of hexachlorocyclopentadiene: subchronic (13-week) administration by gavage to F344 rats and B6C3F1 mice.
A 13-week subchronic study was conducted by administering hexachlorocyclopentadiene ( HCCP ) in corn oil by gavage to groups of ten male and ten female F344 rats at doses of 150, 75, 38, 19, 10 or 0 mg kg-1, and to groups of ten male and ten female B6C3F1 mice at doses of 300, 150, 75, 38, 19 or 0 mg kg-1. The doses were administered once a day, five days per week for 13 weeks. Chemically induced deaths occurred at 150 and 300 mg kg-1 in rats and at 300 mg kg-1 in mice. A significant (P less than 0.05) depression in mean body-weight change relative to controls was observed in male and female rats receiving greater than or equal to 38 and greater than or equal to 75 mg kg-1, respectively, and in male and female mice receiving 150 and 300 mg kg-1, respectively. There was a significant (P less than 0.05) increase in liver and kidney weight: brain weight ratios in the high-dose female rats (75 and 150 mg kg-1) and female mice at all doses (19-300 mg kg-1). HCCP caused proliferative and inflammatory changes of the epithelia in the forestomach of male rats, and male and female mice receiving greater than or equal to 38 mg kg-1 and in female rats receiving greater than or equal to 19 mg kg dose level. Nephrosis characterized by proximal tubular dilation, cytoplasmic vacuolization, cytomegaly, karyomegaly and anisokaryosis occurred in male and female rats and female mice receiving greater than or equal to 38 mg kg-1.
Animals↗
Encephalopathy in rats and nephropathy in rats and mice after subchronic oral exposure to benzaldehyde.
Male and female Fischer 344 rats and B6C3F1 mice were treated daily (5 days/wk) with benzaldehyde by gavage either in 12 doses of 0 (vehicle control), 100 (rats only), 200, 400, 800, 1600 or (for mice only) 3200 mg/kg body weight/day (followed by 2 days' observation without treatment), or for 90 days in doses of 0, 50, 100, 200, 400 or 800 mg/kg/day (rats) or 0, 75, 150, 300, 600 or 1200 mg/kg/day (mice). In the acute studies, benzaldehyde induced deaths and decreased body-weight gain in both sexes of rats given 800 or 1600 mg/kg/day and caused deaths in both sexes of mice given 1600 or 3200 mg/kg/day. In the 90-day studies, deaths occurred in both sexes of rats on 800 mg/kg/day and in male mice on 1200 mg/kg/day. Body-weight gain was depressed in male rats on 800 mg/kg/day, in male mice on 600 mg/kg/day and in female mice on 1200 mg/kg/day. Necrotic and degenerative lesions were seen in the cerebellar and hippocampal regions of the brain in both sexes of rats given 800 mg/kg/day, but not in mice. Renal tubular necrosis occurred in male and female rats on 800 mg/kg/day and in male mice on 1200 mg/kg/day. Mild epithelial hyperplasia or hyperkeratosis of the forestomach was seen in male and female rats on 800 mg/kg/day. In this limited study, the no-observed-toxic-effect doses of benzaldehyde administered by gavage were 400 mg/kg/day in male and female rats, 300 mg/kg/day in male mice and 600-1200 mg/kg/day in female mice.
Administration, Oral↗
Natural history of potassium-deficiency myopathy in the dog: role of adrenocorticosteroid in rhabdomyolysis.
Potassium deficiency occurs in several conditions and is reported to cause muscle weakness and rhabdomyolysis. The mechanisms by which potassium deficiency cause muscle disease remain unknown, but the primary purpose of the present study was to determine whether abnormal muscle glycogen metabolism causes muscle weakness, as suggested by previous work. We monitored the natural history of potassium deficiency in two groups of dogs, one of which also received deoxycorticosterone acetate (DOCA), an agent commonly used in other studies to accelerate potassium loss. Group I dogs on potassium-free diet alone showed a 41% decrease in muscle potassium, no change in serum CO2, creatine kinase (CK), or muscle phosphorylase activity and only mild histopathologic abnormalities before death, after 198 +/- 42 days on the diet (mean +/- S.D.). In contrast, group II dogs on the same diet plus DOCA developed clinically similar severe weakness and died more rapidly than group I, 37 +/- 7 days (p less than 0.03). DOCA dogs showed a more rapid decrease in muscle potassium to the same level as group I, a 37% increase in serum CO2, an increase in serum CK to 1060 to 2775 IU/ml, a 23% decrease in muscle phosphorylase activity, and severe muscle histopathology, including rhabdomyolysis. Neither group showed any change in body weight, electromyogram (EMG), muscle glycogen concentration, glycogen synthetase activity, serum or muscle magnesium or phosphorus, or serum T3 or T4. In conclusion, dietary potassium deficiency in dogs causes severe weakness and death without causing rhabdomyolysis or abnormal muscle glycogen metabolism. Adding DOCA to the potassium-free diet creates a different model characterized by rapid clinical deterioration and rhabdomyolysis.
Animals↗
Leiomyosarcoma of the canine urinary bladder, with metastases.
An enlarged nodular mass, assumed to be the prostate gland because of location and consistency, was palpated in the pelvic region of a 10-year-old German Shepherd Dog. Castration was performed as a therapeutic procedure after an estrogenic hormone failed to reduce the size of the mass. A tumor identified histologically as a seminoma was in the right testicle. The dog died 1 month after castration, and generalized metastatic neoplasia was observed at necropsy. The mass that involved the neck of the bladder and the metastases were identified as leiomyosarcoma.
Animals↗