Rg. Struble et M. Ghobrial, CANCER-TREATMENT AND GROWTH CONE-ASSOCIATED PROTEIN IN HUMAN OLFACTORY-BULB GLOMERULI, Archives of otolaryngology, head & neck surgery, 124(8), 1998, pp. 867-870
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.