Apparent synergism between radiation and the carcinogen 1,2-dimethylhydrazine in the induction of colonic tumors in rats

John G Sharp, D. A. Crouse

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We have evaluated the interaction of radiation and 1,2-dimethylhydrazine (DMH) with respect to colon carcinogenesis in the Fischer 344 rat and have demonstrated the utility of this model for future more detailed mechanistic studies. In initial experiments, single doses of abdomen-only radiation (9 Gy) or DMH (150 mg/kg) were employed alone or in combination. Radiation was administered 3.5 days prior to the DMH. At 8 months post-treatment, the incidence of DMH-induced colon tumors was doubled by prior radiation exposure. When the protocol was repeated employing a DMH dose of 135 mg/kg with a 6-month observation period, the incidence of tumors induced by DMH alone was reduced, but the combination of radiation plus DMH still resulted in an augmentation of tumor incidence. When the protocol of radiation plus DMH was repeated three times at monthly intervals, a 15-fold increase in tumor incidence (from 5 to 74%) was observed at 6 months post-treatment. This finding demonstrates an apparent synergy between the radiation and the chemical carcinogen. Throughout these studies, the appearance of carcinomas was associated with preexisting colonic lymphoid nodules. The reproducibility of tumor induction as well as range of tumor incidence generated by variations in this system may be adequately sensitive to examine the combination of much lower doses of radiation and/or chemical carcinogen. The relationship between existing lymphoid aggregates which alter local epithelial cell kinetics and which are associated with fenestrations in the basement membrane, and the development of colon cancer in congruent sites may assist in defining dose-response curves for combined agents as well as providing a system for evaluating the mechanisms underlying their interactions.

Original languageEnglish (US)
Pages (from-to)304-317
Number of pages14
JournalRadiation Research
Volume117
Issue number2
DOIs
StatePublished - Jan 1 1989

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dimethylhydrazines
Dimethylhydrazines
1,2-dimethylhydrazine
1,2-Dimethylhydrazine
carcinogens
synergism
Carcinogens
rats
induction
tumors
Radiation
neoplasms
incidence
radiation
Neoplasms
Incidence
dosage
colon
Colon
cancer

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Cite this

Apparent synergism between radiation and the carcinogen 1,2-dimethylhydrazine in the induction of colonic tumors in rats. / Sharp, John G; Crouse, D. A.

In: Radiation Research, Vol. 117, No. 2, 01.01.1989, p. 304-317.

Research output: Contribution to journalArticle

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