DNA repair synthesis and chromosomal aberrations induced in vivo by triethylenemelamine

The alkylating agent, triethylenemelamine (TEM), was studied for its ability to induce unscheduled DNA (repair) synthesis (UDS) in vivo in rat lymphocytes. Somatic cytogenetic alterations were analyzed (in bone marrow) and compared with UDS as a function of TEM dosage. UDS was evaluated through the use of autoradiography; cytogenetic alterations were studied in metaphase bone marrow chromosome preparations.Data indicated that the degree of UDS is a direct function of TEM dosage up to a rate-limiting concentration, at which point it ceases to be dose dependent. Except for a deviation at the highest dose level tested, the extent of cytogenetic damage was directly and linearly related to TEM dose. Between the control and intermediate (0.2 mg/kg) dose levels, UDS response increased II-fold while cytogenetic damage showed only a 4-fold increase; this disparity diminished with increasing TEM dose. In the lower dose levels, therefore, the greater relative sensitivity of UDS evaluation in the detection of genetic activity may be indicated. Patterns of UDS response observed through the in vivo assay developed in this study were found to be analogous to those established in in vitro studies.