Preclinical studies with triazinate (NSC-139105), an antifolate drug, in beagle dogs and rhesus monkeys.

Preclinical studies with triazinate (NSC-139105), an antifolate drug, in beagle dogs and rhesus monkeys. Research Abstract Details 

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Preclinical studies with triazinate (NSC-139105), an antifolate drug, in beagle dogs and rhesus monkeys. Abstract Text:

E J Gralla,G L Coleman,W Osbaldiston,W L Sawicki,R M Jonas,J R Bertino,

The effects of the intravenous administration of triazinate by single and multiple injections were studied in beagle dogs and rhesus monkeys. In dogs, dose levels ranging from 0.3125 to 40 mg/kg were given either as single doses daily for 5 days, or once weekly for 6 weeks. The 5-day regimen was also studied in monkeys with dose levels from 2.5 to 40 mg/kg/day. Prominent drug-related and drug-dependent effects which appeared in both species were piloerection, muscular weakness, and respiratory difficulty which occurred during and immediately after the administration of dose levels of 10 mg/kg or greater. Gastrointestinal toxicity was severe in dogs but mild in monkeys. Lymphoid tissue toxicity was manifested by a circulating lymphopenia and localized cellular depletion in the germinal centers of lymphoid tissues. In dogs, signs of bone marrow toxicity consisted of a circulating neutropenia and, at necropsy, a reduction in the number of erythroid and myeloid elements plus megaloblastosis. Only the latter change was observed in monkeys. This difference in the hematopoietic toxicity between the beagle dog and the rhesus monkey was corroborated by the findings from in vitro studies with bone marrow. DNA synthesis in beagle bone marrow cells was depressed significantly by triazinate as compared with cells from rhesus marrow. A direct renal toxic effect was observed in monkeys given high doses of triazinate (20 and 40 mg/kg/day or 240-280 mg/m/day) for 5 days.

Preclinical studies with triazinate (NSC-139105), an antifolate drug, in beagle dogs and rhesus monkeys. Publishing Authors By Initials

EJ Gralla,GL Coleman,W Osbaldiston,WL Sawicki,RM Jonas,JR Bertino,

For similar heterocyclic compounds: heterocyclic compounds, 1-ring: triazines research abstracts see: heterocyclic compounds: heterocyclic compounds, 1-ring: triazines research

PUBMED ID PMID:

MEDLINE DATE: 1975 May-Jun

Preclinical studies with triazinate (NSC-139105), an antifolate drug, in beagle dogs and rhesus monkeys. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer chemotherapy reports. Part 1

VOLUME: 59

Page Numbers: 523-30

Journal Abbreviation:

ISSN: 0069-0112

DAY: 20

MONTH: 02

YEAR: 2008

Preclinical studies with triazinate (NSC-139105), an antifolate drug, in beagle dogs and rhesus monkeys. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7607105

Preclinical studies with triazinate (NSC-139105), an antifolate drug, in beagle dogs and rhesus monkeys. Keywords Mesh Terms:

KEYWORDS: Triazines

MESH TERMS: toxicity

Chemical & Substance for Abstract: Preclinical studies with triazinate (NSC-139105), an antifolate drug, in beagle dogs and rhesus monkeys. Information

Substance Name: DNA

Registry Number: 9007-49-2

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Country: UNITED STATES

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MEDLINETA: Cancer Chemother Rep

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