Search PubMed⌕ Search

Biomedical subjects

M C Henry

Publications and source records attributed to M C Henry.

At least 73 records · Page 4Linked to original sources

Nephrotoxic potential of cis-diamminedichloroplatinum and four analogs in male Fischer 344 rats.

Cis-diamminedichloroplatinum [cis-DDP; NSC-119875] and four analogs (NSC-241240, NSC-271674, NSC-263158, and NSC-268252) were evaluated for their acute nephrotoxic potential in male F344 rats following iv administration. Indices of nephrotoxicity included blood urea nitrogen, serum creatinine, kidney weights, and microscopic examination. Results indicated that renal function, organ weights, and histology are important criteria for assessing the nephrotoxic potential of cis-DDP analogs, although alterations in these parameters may have been influenced by severe body weight loss. cis-DDP appeared to be the most nephrotoxic compound studied, and NSC-241240 demonstrated minimal renal damage. Ranking of compounds in order of their nephrotoxic potential (most to least) was cis-DDP, NSC-263158, NSC-268252, NSC-271674, and NSC-241240.

Animals↗

Toxicologic evaluation of streptozotocin (NSC 85998) in mice, dogs and monkeys.

Single intravenous doses of CDF1 mice, and single and five daily intravenous treatment schedules in beagle dogs and rhesus monkeys were used to evaluate the toxicity of Streptozotocin (SZN). The major target organs in the three species were liver, kidney, lymphoid tissue and pancreatic islet beta cells. Moderate bone marrow depression and gastrointestinal toxicity were observed in the large animal species after lethal doses. Monkeys were less sensitive than the dog to the hepatotoxic effects of SZN and clinical signs of liver dysfunction were more severe in dogs after multiple doses. Microscopic lesions in the renal proximal convoluted tubules were present in the three species; these lesions appeared to be irreversible for dogs. The toxic effect on the endocrine pancreas was manifest by hyperglycemia, glucosuria, islet atrophy and beta cell degranulation. Multiple dose regimens were less toxic than single doses in dogs and monkeys in terms of the total dose received.

Animals↗

Preclinical toxicologic evaluation of ICRF-187 in dogs.

Single- and multiple-treatment schedule in dogs were used to evaluate the toxicity of ICRF-187. The major target organs were the bone marrow, lymphoid tissue, gastrointestinal tract, liver, and kidney. Liver, kidney, and intestinal toxic effects were most severe at lethal doses. Toxic effects on the kidney and intestinal tract were reduced or absent at lower doses. Hepatotoxicity was most severe after single doses and was only slowly reversible at high doses. Repeated dosage regimens had the greatest effect on circulating blood cells, and anemia and neutropenia were most prominent after three series of five daily doses with rest periods between series. ICRF-187 was more toxic to dogs in terms of total dose received when administered in five daily doses than in single doses. A rest period between series of five daily doses allowed a larger total dose to be administered.

Animals↗

Toxicity of spirogermanium in mice and dogs after iv or im administration.

Toxicity of single-dose spirogermanium was evaluated after iv and im administration to CDF1 mice and beagle dogs. The im LD50 in mice was approximately threefold greater than the iv LD50. The lethal dose in dogs was the same for both routes of administration, but death was delayed after im injection. Convulsive seizures occurred only after the im doses that were lethal, but they were observed after administration of iv doses that were nonlethal. Microscopic evidence of drug toxicity (necrosis and degeneration) was found in mitotically active tissues: intestinal tract, lymphoid tissue, and bone marrow. Necrosis, hemorrhage, edema, and granulation tissue were observed in the muscle injection site.

Animals↗

Effect of particle size distribution on hexamethylmelamine toxicity in rats.

Single oral dose toxicities of six hexamethylmelamine samples with different particle size distributions were evaluated in Osborne-Mendel rats. The calculated LD50 values for the 6 samples were 1706 to 2150 mg/kg )10,236 to 12,900 mg/m2). The two samples with median particle size less than 40 micron were more toxic than the other 4 samples. Among the latter samples, severity of toxic effects was not correlated with particle size. Leukocytes, lymphocytes, platelets and body weight showed dose-related decreases for all samples. Particle size appeared to have a minimal effect on these variables. The drug produced toxic effects on rapidly proliferating tissues: lymphoid, hematopoietic and germinal epithelium. At lethal doses, microscopic lesions were lymphoid tissue hypoplasia, bone marrow hypoplasia with elevated myeloid:erythroid ratios and spermatogenic arrest. The major target organs at nonlethal doses were bone marrow and germ cells, with germinal epithelium showing the most severe lesions.

Altretamine↗

Effect of anesthetic agent on lung tumor induction in hamsters given benzo[a]pyrene-ferric oxide.

The effects of an anesthetic agent on lung tumor induction in noninbred Syrian golden hamsters were investigated after intratracheal instillation of a benzo[a]pyrene-ferric oxide mixture. Inhalation anesthesia with ether or methoxyflurane was accomplished with a closed recirculatory system that allowed a short induction time for anesthesia and a good control over the concentration of anesthetic. This type of anesthetic induction was compared with systemic induction by Brevital. Survival rates during the 10 weekly instillations were least for the Brevital-treated group and greatest for the methoxyflurane-treated group. Body weight gain was lower in both the ether- and Brevital-treated groups as compared to the group anesthetized with methoxyflurane. The animals anesthetized with Brevital had the shortest tumor latency, but the tumor incidence during the weeks of the experiment was similar in the group treated with this agent and the group treated with ether. Exposure to methoxyflurane and the carcinogen produced a slow onset of deaths from tumors and lower tumor incidence. These results are discussed in relation to retention of the dose of carcinogen in the respiratory tract and effect of inhalation anesthia on consequent lung tissue pathology.

Anesthetics↗

Importance of physical properties of benzo(a)pyrene-ferric oxide mixtures in lung tumor induction.

Three mixtures of benzo(alpha)(a)pyrene (BP) and ferric oxide with different physical properties were given intratracheally to Syrian golden hamsters for an examination of their neoplastic potential. Hamsters treated with a preparation containing large aggregates of BP and ferric oxide resulting from nucleation of BP on the particles showed an earlier onset and higher incidence of respiratory tract tumors than animals given a mixture containing smaller aggregates prepared by hand-grinding. The greatest number of tumors were present in the trachea and the predominant type was the squamous carcinoma. A third preparation in which the carcinogen was not attached to the ferric oxide showed a low tumor incidence similar to that present after intratracheal intubation of BP in gelatin without a carrier particle. For this model system of respiratory carcinogenesis, the physical attachment of BP and the carrier dust is necessary for a high tumor yield.

Animals↗