Alkylnitrosoureas, because of their chemical simplicity and known catabolism as well as their ability to induce a high incidence of neurogenic tumors with precision, provide an excellent opportunity to study the mechanism of induction and pathogenesis of neoplasms. This project utilizes marked variations in susceptibility and length of latency peroids observable between rat strains during transplacental induction of neurogenic tumors with ethylnitrosourea. Attempts will be made to correlate such variations in carcinogenic susceptibility with differing activities of gene processing by examining synthesis and induction of helix destabilizing protein and rec?-like protein in glial (target) and neuronal (non-target) cells of carcinogenically susceptible and resistant strains of rats. The precision of ethylnitrosourea in the neurogenic tumor induction will further be utilized in evaluating the role of nerve growth factor in regression of trigeminal neurinoma. It is also proposed to produce trigeminal neurinoma clones with nerve growth factor receptors, which will be used to further examine the morphological and biological effects of nerve growth factor upon anaplastic tumor cells of neural crest derivation.
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