Induction of prolactin-deficient variants of GH3 rat pituitary tumor cells by ethyl methanesulfonate: reversion by 5-azacytidine, a DNA methylation inhibitor.

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Abstract
GH3 cells are a rat pituitary tumor line expressing prolactin (rPRL) and growth hormone. The DNA alkylating agent ethyl methanesulfonate can induce the appearance of rPRL-deficient GH3 cell variants at a high frequency (.apprx. 20-30%). Such variants cannot be induced at high frequency by irradiation of wild-type GH3 cells with UV light, indicating that the effect may be specific to treatment with alkylating agents. The DNA methylation inhibitor 5-azacytidine reverted an ethyl methanesulfonate-induced rPRL-deficient variant into rPRL-expressing cells at high frequency (.apprx. 50%). The revertants were stable for at least 30-35 generations. The alkylating agent may promote the specific methylation of the rPRL gene or a gene regulating its activity, either one of which leads to inactivation of expression of the rPRL gene in GH3 cells.