Differential DNA damage induced by chemical mutagens in cells growing in a modified Selye's granuloma pouch

Abstract

Rapid growth of granulation tissue was induced in rats by injection of croton oil into a subcutaneous air pocket. Growth characteristics of the granulation tissue were evaluated by histopathologic techniques and measurement of 3H-thymidine incorporation into DNA. The DNA of cells growing in the granuloma was labeled with 3H-thymidine. Subsequently, 4 classes of test chemicals (monofunctional and polyfunctional alkylating agents, DNA intercalating agents and chemicals not known to interact with DNA) were injected intraperitoneally. The presence of single-strand breaks was assayed in DNA of granuloma tissue using the alkaline elution technique. DNA breaks were primarily induced by monofunctional alkylating agents and were characteristic for each compound. DNA from animals treated with polyfunctional alkylating agents and DNA-intercalating agents showed a variable degree of resistance to methylmethane sulfonate-induced DNA breakage.