Studies of DNA-strand induced in human fibroblasts by chemical mutagens/carcinogens.

A method for the study of DNA-strand breaks using alkaline denaturation followed by hydroxylapatite chromatography has been modified and used for the detection of chemically induced DNA-strand breaks. A new procedure for the incubation of human fibroblasts with a metabolizing system and the detection of DNA-strans breaks is presented. With this method the induction and repair of DNA-strand breaks have been studied in human fibroblasts exposed to methyl methanesulphonate, melphalan, benzo[a]pyrene and cyclophosphamide. These agents all give rise to DNA-strand breaks. In cells exposed to methyl methanesulphonate, melphalan or benzo[a]pyrene these breaks disappeared within 21 h after re moval of the drug. In cells exposed to the bifunctional alkylating agent cyclophosphamide, studies of DNA-strand breaks suggest the presence of inter-strand cross links.