SPLTRAK Abstract Submission
(Cyclophosphamide-induced TNFα expression in the taste buds: Cytoprotective effect of Amifostine. )
Anish Sarkar1, David Allyn2, Rona Delay3, Eugene Delay4
1The University of Vermont, Burlington, VT, United States
2University of Pennsylvania, Philadelphia, PA, United States
3The University of Vermont, Burlington, VT, United States
4The University of Vermont, Burlington, VT, United States

Chemotherapy is a predominant mode of cancer treatment in patients, often inducing adverse effects such as taste dysfunctions when the drug also affects normal tissues. Disturbances in taste can result in malnutrition, weight loss and further aggravate the condition of the patient during recovery. There could be various reasons for drug-induced taste disturbances such as loss of cells within taste buds, disruptions in taste cell renewal, and tissue inflammation. Our lab has been studying the molecular, cellular and behavioral effects of the chemotherapy drug, cyclophosphamide (CYP). CYP is an antineoplastic, which is a pro-drug and inactive in its native state. Once it is metabolized in the liver by the P450 enzyme complex, its primary metabolite, phosphoramide mustard, functions as an alkylating agent. Our current research is focused on potential CYP-induced inflammation. Specifically, this study is examining the expression of the cytokine TNFα in the taste bud during the 72 h timeline, immediately after injection as well as determine if Amifostine offers any protection to taste buds. Previous research using TUNEL and caspase-3 assays suggests CYP-induced cell loss in fungiform and circumvallate papillae peaks at about 8 and again 18-24 h, post-CYP administration (75 mg/kg, IP). Our present investigation using immunohistochemical analysis suggests that the peak expression of the pro-inflammatory cytokine, TNF-alpha occurs about 8 and 24 hrs post CYP injection in both fungiform and circumvallate papillae. Pre-treatment (100 mg/kg, SC) with Amifostine, appears to decrease the expression of TNF-alpha, indicating the drug can protect the taste system from the alkylating effects of CYP metabolites