Clark, John M.Strycharz, Joseph P2024-04-262010-03-122010-05510.7275/1219623https://hdl.handle.net/20.500.14394/47308Resistance to dichlorodiphenyltrichloroethane (DDT) in the 91-R strain of Drosophila melanogaster is extremely high compared to the susceptible Canton-S strain (>1500 times). Oxidative detoxification is involved in resistance but is not the only mechanism. Rates of DDT penetration, metabolism, and excretion were determined radiometrically between resistant 91-R and susceptible Canton-S strains. Contact penetration was ~1.5-times slower with 91-R flies compared to Canton-S flies. The 91-R strain had 13-fold more cuticular hydrocarbons, possibly resulting in penetration differences. DDT was metabolized ~33-fold more extensively by 91-R than Canton-S resulting in dichlorodiphenyldichloroethane (DDD), two unidentified metabolites and polar conjugates being formed in significantly greater amounts. 91-R also excreted ~5.0 times more DDT and metabolites than Canton-S. Verapamil pretreatment reduced the LD50 value for 91-R flies topically dosed with DDT by a factor of 10-fold. Thus, it is likely that the increased excretion by 91-R flies is due to the increased expression of ATP-binding cassette (ABC) transporter genes, including MDR50 (CG8525) that had a 36% higher transcript level by quantitative real time PCR than Canton-S flies. In summary, DDT resistance in 91-R is polyfactorial and includes reduced penetration, increased detoxification and direct excretion.ToxicologyDDTDrosophilaResistanceMetabolismP-glycoproteinBiotechnologyThesis (Open Access)