1,3-, 1,6-, and of 1,3-and 1,6-DNP, but not 1,8-DNP, was signifi-1,8-DNP) are direct-acting mutagens in that they do cantly (P õ 0.05) increased in the Ames assay while not require an exogenous source of enzymes for the mutagenicity of the three DNPs was increased activation to mutagens in the Ames assay. However, in the umu assay. Also, a biphasic response was the addition of mammalian S9 preparations, or the observed in the umu assay with 1,6-and 1,8-DNP, microsomal and cytosolic compartments comprising in that AR-cytosol enhanced the mutagenicity at low S9, modulate the mutagenic response of these protein concentrations (5 -50 mg protein/reaction) DNPs. In this study, we compared the mutagenic but abrogated the response at higher protein conresponse of these DNPs in the presence of cytosol centrations. The effect of cytosol from control rats and microsomal fractions from the liver of Aroclor-depended on the isomer tested; 1,3-DNP was actipretreated (AR) and control rats, in the Ames muta-vated above the background level in both assays genicity assay and umu gene induction assay. 1,3-(nearly twofold) while 1,6-DNP and 1,8-DNP were and 1,8-DNP were deactivated to a greater extent only activated at low protein concentrations in the by microsomes from AR-induced and control rats umu assay. In the Ames assay, cytosol from ARthan was 1,6-DNP, in both the umu and Ames pretreated rats did not alter the mutagenic response assays. In the Ames assay, S9 was more potent in with 1,8-DNP, while control cytosol significantly (P deactivating the DNP than an equivalent concentra-õ 0.05) deactivated 1,8-DNP at all substrate contion of microsomes from the same S9 preparation. centrations tested. In summary, this study showed Also, S9 from AR-pretreated rats deactivated the that the mutagenicity of 1,3-DNP was similar in the isomers to a greater extent than S9 from control two assays but the responses with 1,6-and 1,8rats. In contrast to the constant deactivation of all DNP differed in the two assays. These isomeric difthe isomers in the two assays catalyzed by micro-ferences could be due to the varying metabolic pathsomes and S9, the response with cytosol from AR-ways of the three DNPs as well as the detectable pretreated rats differed with respect to the three iso-end points of the two assays. Environ. Mol. Mutamers in the Ames and umu assays. When cytosol gen. 30:303-311, 1997.