DNA damage caused by etoposide and gamma-irradiation induces gene conversion of the MHC in a mouse non-germline testis cell line

We have explored the effects of gamma-irradiation and etoposide on the gene conversion frequency between the endogenous major histocompatibility compl ex class II genes Abk and Ebd in a mouse testis cell line of non-germline o rigin with a polymerase chain reaction assay. Both gamma-rays and etoposide were shown to increase the gene conversion frequency with up to 15-fold co mpared to untreated cells. Etoposide, which is an agent that stabilise a cl eavable complex between DNA and DNA topoisomerase Il, shows an increased in duction of gene conversion events with increased dose of etoposide. Cells t reated with gamma-rays, which induce strand breaks, had an increased gene c onversion frequency when they were subjected to low doses of irradiation, b ut increasing doses of irradiation did not lead to an increase of gene conv ersion events, which might reflect differences in the repair process depend ing on the extent and nature of the DNA damage. These results where DNA dam age was shown to be able to induce gene conversion of endogenous genes in m ouse testis cells suggests that the DNA repair system could be involved in the molecular genetic mechanism that results in gene conversion in higher e ukaryotes like mammals. (C) 1999 Elsevier Science B.V. All rights reserved.