MECHANISMS INVOLVED IN 6-THIOGUANINE-INDUCED REVERSAL OF IMMUNOGENICITY OF L1210 DTIC LEUKEMIC LINE/

We investigated two possible mechanisms of action of 6-Thioguanine (6- Tg) in a phenomenon recently observed in our laboratory, namely the re versal of drug-induced immunogenicity in L1210 murine leukemia by <<in vitro>> treatment with 6-thioguanine. The first experimental approach was a comparative study of the action of 6-Tg on the highly tumorigen ic L1210 murine leukemia and on the poorly tumorigenic (immunogenic) L 1210/DTIC subline. Our results demonstrated that, even if the L1210 le ukemia has a rate of <<spontaneous>> mutants at HPRT locus greater tha n the immunogenic counterpart its tumorigenicity is not correlated wit h the expression of HPRT locus. So far, the recovery of tumorigenicity induced by 6-Tg on L1210/DTIC cell line is unlikely to be the result of a selection of HPRT- cells. The second experimental approach was di rected to investigate a possible hypomethylating action of 6-Tg. Sever al clones derived from L1210/DTIC cell line after <<in vitro>> treatme nt with 5-azacytidine and 5-bromodeoxyuridine (respectively hypo and h ypermethylating agents) were screened for the expression of the surfac e antigens defined by Mab C3B/D and L.2. Some clones were also employe d in a tumorigenicity test. The results of our experiments demostrated that neither the hyper nor the hypomethylating treatments are capable of reverting the immunogenicity of the L1210/DTIC cell line.