Directed, heritable alterations in gene expression, called epigenetic changes, have been proposed as a basic mechanism for tumor transformation. The major objectives of his proposal are: to find out to what extent epigenetic changes in the production of specific growth factors can account for autonomous growth, tumor progression, and tumor reversal in plants; and, to find molecular mechanisms for these changes. Earlier we found that heritable changes in the growth-factor production of normal and crown-gall tumor cells of tobacco could be induced and reversed at will in culture. Using this and related cell culture models we plan to test two hypotheses: First, that tumor inception and progression involves the perturbation of normal cells to give a diverse population of heritably altered cells followed by the selective proliferation of those cells with the capacity for autonomous growth. Second, that the persistent production of growth factors by tumor cells is maintained by a positive-feedback loop in which these factors induce their own production or inhibit their own degradation.