Effects of dichlorodiphenyltrichloroethane and its analogues on rat liver mitochondria.

The effects of dichlorodiphenyltrichloroethane (DDT) and sixteen analogues on respiration, swelling and latent ATPase of rat liver mitochondria were examined systematically. The compounds tested could be divided into four groups: DDT-type, DDE-type, kelthane-type and others by substituent groups on the ethane bridge of bis(p-chlorophenyl) ethane. Most compounds tested were shown to inhibit State 3 respiration. A linear relation was observed between the logarithms of the concentrations giving half-inhibition of State 3 respiration and the logarithms of the partition coefficients of the tested compounds. Four compounds of the kelthane type and chlorobenzilate stimulated State 4 respiration to the level of dinitrophenol-stimulated respiration. The compounds that have a hydroxy group on the ethane bridge-rapidly induced mitochondrial swelling, but DDT-type and DDE-type compounds induced swelling when the suspension contained 0.15 M KCl and 5 mM Tris-HCl. Latent ATPase of mitochondria was stimulated to different maximum levels by each of the tested compounds except DDA. The oligomycin-sensitive ATPase of submitochondria was inhibited by a series of kelthane-type compounds.