Transformation of human leukocytes with Epstein-Barr virus after cellular exposure to chemical or physical mutagens.

Assays that quantitate leukocyte transformation were used to determine the effect of two chemical and two physical mutagens on Epstein-Barr virus (EBV)-induced transformation of human umbilical cord leukocytes (HUCL). After treatment of HUCL with methyl methanesulfonate (MMS). UV light, or X-rays, lymphocyte transformation by EBV displayed a typical "survival" curve usually associated with agent toxicity in dividing cell populations. Viral transformation showed increasing resistance to each of these agents if the lymphocytes were treated after virus infection. No enhancement of viral transformation was detected following MMS, X-ray, or UV treatment. In contrast, after sublethal doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were administered, HUCL were more readily transformed by exogenous EBV. Also, in direct contrast to the other mutagens tested, EBV-induced transformation became markedly more sensitive to MNNG when leukocytes were treated after virus infection. Neither chemicals nor radiation alone was capable of initiating HUCL transformation, nor could infectious EBV be routinely recovered from transformed HUCL treated with MNNG or radiation. These results suggest that MNNG enhanced transformation by predisposing leukocytes toward transformation during EBV infection.