High rate of morphological reversion in tumor cell line H-19 associated with permanent transcriptional suppression of the LTR, v-src, LTR provirus

Abstrad The highly malignant line of morphologically transformed H-i 9 hamster tumor cells that harbor a single LTR, v-src, LTR provirus segregates morphologically flat revertants at the rate of 1 .4 to 2.4 x 1 03/cell/cycle. Revertants behave like almost nonmalignant cells; they keep the provirus within an unaltered jundion DNA fragment. However, the provirus is methylated, permanently transcriptionally silent, and not rescuable. Using the polymerase chain readion, we have synthesized the whole proviral strudure from two revertants and established that the left-hand long terminal repeats assuring transcription remained strudurally intad. Moreover, the cloned proviral DNAs from three revertants were shown to produce tumors in chickens. The unusually high reversion rate together with the finding of strudural integrity of proviral transcriptional signals in revertants indicate strongly that the reversion has been mediated by cell-regulatory mechanisms.