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. Disruption of regeneration should be evidenced by decreased presence of growing axons in the olfactory bulb.


OBJECTIVE
To evaluate GAP43 in human olfactory bulb in normal controls and in individuals receiving treatment for neoplasms.


METHODS
Immunocytochemical studies were performed on autopsied human olfactory bulbs to identify both GAP43 and olfactory marker protein immunoreactivity. The former recognizes growing axons and the latter is a definitive marker of adult olfactory nerve.


METHODS
Twenty-seven subjects were evaluated. Seven had received either antineoplastic agents and/or x-irradiation of the whole head. Four subjects were young, untreated controls, 10 were age matched to the treated group, and 2 had neoplasms but did not receive antineoplastic agents or irradiation of the head. In addition, 3 subjects with end-stage renal disease were immunostained.


RESULTS
Subjects treated with antineoplastic agents or x-irradiation of the whole head displayed no statistically significant loss of olfactory bulb glomeruli, but GAP43 immunoreactivity was markedly reduced in all but 1 subject (P<.32). The subjects with end-stage kidney disease showed frank loss of both GAP43 immunoreactivity and olfactory glomeruli.


CONCLUSIONS
Treatment with antineoplastic agents apparently does not damage olfactory epithelium directly but inhibits growth of new axons into the olfactory bulb. This observation suggests that the quality of olfactory experience may change during the course of treatment with antineoplastic agents because the olfactory nerve is not replaced.
Struble
R G
RG
Center for Alzheimer Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield 62794-1413, USA. bstruble@neuro.siumed.edu
Ghobrial
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001369:Axons / Q000187:drug effects; D001932:Brain Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000532:radiotherapy; D005260:Female; D019922:GAP-43 Protein / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009416:Nerve Regeneration / Q000187:drug effects; D009830:Olfactory Bulb / Q000737:chemistry* / Q000473:pathology; D018035:Receptors, Odorant / Q000187:drug effects
D000970:Antineoplastic Agents; D019922:GAP-43 Protein; D018035:Receptors, Odorant