Dinitrotoluene structure-dependent initiation of hepatocytes in vivo

Technical grade dinitrotoluene (TDNT), composed principally of 2,4-DNT (76%) and 2,6-DNT (20%), is a potent hepatocarcinogen when fed to male F-344 rats for 1 year (100% incidence of hepatocellular carcinoma) while 2,4-DNT is only weakly hepatocarcinogenic. The present investigation was designed to determine the relative initiating potential of DNT isomers compared with the initiating potential of TDNT. A single administration of either TDNT or 2,6-dinitrotoluene (75 mg/kg, p.o.), in combination with partial hepatectomy, initiated hepatocytes in rats when assayed using hepatic initiation-promotion protocols. Five other DNT isomers (2,3; 2,4; 2,5; 3,4, and 3,5-DNT) evaluated similarly exhibited no such potential. Although 2,6-DNT was a relatively weak initiator, its activity was comparable to the initiating activity detected in TDNT. These data begin to provide an explanation for the marked differences in the hepatocarcinogenic potency of TDNT and 2,4-DNT observed in independent 2 year bioassays.