Carcinogenicity of the antineoplastic agent, 5 (3,3 dimethyl 1 triazeno) imidazole 4 carboxamide, and its metabolites in rats

D. D. Beal, J. L. Skibba, W. A. Croft, Samuel Monroe Cohen, G. T. Bryan

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Abstract

Chronic oral administration of the antineoplastic agent, 5 (3,3 dimethyl 1 triazeno)imidazole 4 carboxamide (DTIC), induced predominantly thymic and mammary tumors as demonstrated previously. Male and female Sprague Dawley and female Buffalo rats were susceptible to the carcinogenicity of DTIC. A 50% incidence of mammary adenocarcinomas was induced in males within 18 weeks. Type of tumor and tumor incidence were dose dependent. Single and multiple intraperitoneal injections of DTIC did not alter organ specificity. DTIC induced thymic lymphosarcomas and mammary adenocarcinomas were transplantable. Tissue distribution studies revealed no correlation between uptake of DTIC by a given tissue and its susceptibility to carcinogenicity. Metabolites of DTIC were tested for carcinogenic activity. Animals administered 5 diazoimidazole 4 carboxamide orally, intraperitoneally, or intragastrically developed low incidences of thymic, stomach, bladder, or mammary tumors. A low incidence of mammary tumors developed in rats fed 2 azahypoxanthine. A variety of tumors, including several ependymoblastomas, were induced in rats that received 5 aminoimidazole 4 carboxamide orally. 5(3 Methyl 1 triazeno)imidazole 4 carboxamide (MTIC), when fed or given in single or multiple intraperitoneal injections, induced a high incidence of mammary adenofibromas and a low incidence of uterine leiomyosarcomas. Control rats had low incidences of mammary adenocarcinomas and adenofibromas after 52 weeks. These data show that the carcinogenic properties of DTIC resemble those of carcinogenic N nitroso compounds, hydrazine, azo, and azoxy alkanes and aryltriazenes and thus suggest similar mechanism(s) of action. These data also indicate that MTIC is involved in the induction of mammary adenofibromas and uterine leiomyosarcoma by DTIC.

Original languageEnglish (US)
Pages (from-to)951-957
Number of pages7
JournalJournal of the National Cancer Institute
Volume54
Issue number4
StatePublished - Dec 1 1975

Fingerprint

Dacarbazine
Antineoplastic Agents
Adenofibroma
Breast
Incidence
Adenocarcinoma
hydrazine
5-(3-methyl-1-triazeno)imidazole-4-carboxamide
Leiomyosarcoma
Breast Neoplasms
Intraperitoneal Injections
Aminoimidazole Carboxamide
Nitroso Compounds
Thymus Neoplasms
Primitive Neuroectodermal Tumors
Neoplasms
Organ Specificity
Alkanes
imidazole-4-carboxamide
Buffaloes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Carcinogenicity of the antineoplastic agent, 5 (3,3 dimethyl 1 triazeno) imidazole 4 carboxamide, and its metabolites in rats. / Beal, D. D.; Skibba, J. L.; Croft, W. A.; Cohen, Samuel Monroe; Bryan, G. T.

In: Journal of the National Cancer Institute, Vol. 54, No. 4, 01.12.1975, p. 951-957.

Research output: Contribution to journalArticle

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abstract = "Chronic oral administration of the antineoplastic agent, 5 (3,3 dimethyl 1 triazeno)imidazole 4 carboxamide (DTIC), induced predominantly thymic and mammary tumors as demonstrated previously. Male and female Sprague Dawley and female Buffalo rats were susceptible to the carcinogenicity of DTIC. A 50{\%} incidence of mammary adenocarcinomas was induced in males within 18 weeks. Type of tumor and tumor incidence were dose dependent. Single and multiple intraperitoneal injections of DTIC did not alter organ specificity. DTIC induced thymic lymphosarcomas and mammary adenocarcinomas were transplantable. Tissue distribution studies revealed no correlation between uptake of DTIC by a given tissue and its susceptibility to carcinogenicity. Metabolites of DTIC were tested for carcinogenic activity. Animals administered 5 diazoimidazole 4 carboxamide orally, intraperitoneally, or intragastrically developed low incidences of thymic, stomach, bladder, or mammary tumors. A low incidence of mammary tumors developed in rats fed 2 azahypoxanthine. A variety of tumors, including several ependymoblastomas, were induced in rats that received 5 aminoimidazole 4 carboxamide orally. 5(3 Methyl 1 triazeno)imidazole 4 carboxamide (MTIC), when fed or given in single or multiple intraperitoneal injections, induced a high incidence of mammary adenofibromas and a low incidence of uterine leiomyosarcomas. Control rats had low incidences of mammary adenocarcinomas and adenofibromas after 52 weeks. These data show that the carcinogenic properties of DTIC resemble those of carcinogenic N nitroso compounds, hydrazine, azo, and azoxy alkanes and aryltriazenes and thus suggest similar mechanism(s) of action. These data also indicate that MTIC is involved in the induction of mammary adenofibromas and uterine leiomyosarcoma by DTIC.",
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