(full paper is archived in the Miller Library)
Title: Musk Ketone, a possible multi-xenobiotic resistance (MXR) modulator as seen in Corbicula fluminea, Lytechinus pictus, Mytilus californianus, and Mytilus edulis
Student Author(s): Chan, Christina
Faculty Advisor(s): Epel, David
Location: Final Papers Biology 175H
Date: June 2000
Abstract: Pharmaceuticals and personal care products (PPCP) have been found in measurable amounts in receiving waters. These non-priority aquatic pollutants may act in unexpected and potentially biohazardous ways. One of the more prevalent PPCPs is a perfume ingredient, musk ketone (1-tert.-butyl-3,5-dimethyl-2,6-dinitro-4-acetylbenzene). I tested musk ketone for its abiltiy to modulate the accumulation and efflux of xenobiotics known to be substrates of the multi-xenobiotic resistant transporter using Corbicula fluminea, Lytechinus pictus, Mytilus californianus, and Mytilus edulis. The multi-xenobiotic resistant transporter (MXR) is a functional homologue of the mammalian multi-drug resistant transporter (MDR), a P-glycoprotein. In aquatic systems, MXR serves as a first line of defense against an array of lipophilic compounds. Musk ketone increased the accumulation of the MXR substrate rhodamine B in L. pictus embryos, and M. californianus gill tissue; initial testing implicated accumulation of rhodamine B in C. fluminea. Musk ketone increased the toxicity of vinblastine-- a MXR substrate that inhibits microtubule formation--in L. pictus, but not in M. edulis embryos. However, musk ketone did not definitely slow the efflux of rhodamine B from L. Pictus and M. californianus suggesting that this chemical is not acting as a classical MXR inhibitor. I condlude that musk ketone is not acting directly on MXR, and must cause accumulation through an alternative, yet to be determined, pathway. Statistical analysis: analysis of variance(ANOVA), and Student-Newman-Keuls test for significant difference, alpha=0.05.