CANCER-TREATMENT AND GROWTH CONE-ASSOCIATED PROTEIN IN HUMAN OLFACTORY-BULB GLOMERULI

Background: Growth cone-associated protein (GAP43) is found in growing axons and we hypothesized that systemic treatment with antineoplastic agents should disrupt regeneration of olfactory receptor cells. Disru ption of regeneration should be evidenced by decreased presence of gro wing axons in the olfactory bulb. Objective: To evaluate GAP43 in huma n olfactory bulb in normal controls and in individuals receiving treat ment for neoplasms. Design: Immunocytochemical studies were performed on autopsied human olfactory bulbs to identify both GAP43 and olfactor y marker protein immunoreactivity. The former recognizes growing axons and the latter is a definitive marker of adult olfactory nerve. Subje cts: Twenty-seven subjects were evaluated. Seven had received either a ntineoplastic agents and/or x-irradiation of the whole head. Four subj ects were young, untreated controls, 10 were age matched to the treate d group, and 2 had neoplasms but did not receive antineoplastic agents or irradiation of the head. In addition, 3 subjects with end-stage re nal disease were immunostained. Results: Subjects treated with antineo plastic agents or x-irradiation of the whole head displayed no statist ically significant loss of olfactory bulb glomeruli, but GAP43 immunor eactivity was markedly reduced in all but 1 subject (P<.32). The subje cts with end-stage kidney disease showed frank loss of both GAP43 immu noreactivity and olfactory glomeruli. Conclusions: Treatment with anti neoplastic agents apparently does not damage olfactory epithelium dire ctly but inhibits growth of new axons into the olfactory bulb. This ob servation suggests that the quality of olfactory experience may change during the course of treatment with antineoplastic agents because the olfactory nerve is not replaced.