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MACROMOLECULAR ADDUCTION BY TRICHLOROACETONITRILE IN THE FISCHER 344 RAT FOLLOWING ORAL GAVAGE
Citation:
Lin, E., T. Reddy, AND F. Daniel. MACROMOLECULAR ADDUCTION BY TRICHLOROACETONITRILE IN THE FISCHER 344 RAT FOLLOWING ORAL GAVAGE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/368 (NTIS PB93107134), 1992.
Description:
Male Fischer 344 rats were administered 1- or 2-[14C]-trichloroacetonitrile (TCAN) by ral gavage. NA was isolated from the liver, kidneys and stomach and several protein fractions (globin, albumin and blobulins) were isolated from blood. CAN binds to both the DNA and the blood proteins in a dose-related manner. ore radiolabel was associated with the DNA when the carbon at C2 position was labeled, than at C1 position. owever, the position of the radiolabel did not influence the levels of radioactivity associated with the blood proteins. he stomach exhibited the highest level of DNA binding, followed in order by the liver and kidney. CAN binding level was higher in DNA isolated from rats killed at 24 hr than at 4 hr after administration. n contract, the three blood proteins showed similar binding levels, regardless of the exposure time. adio-activity associated with DNA was not incorporated into the nitrogen bases (i.e., via de novo synthesis) and a covalent binding index (umole of chemical bound/mole of nucleotide phosphate per mole/kg b.w. of chemical administered) of 30-120 was observed for various tissues. CAN did not bind to calf thymus DNA when directly incubated in a cell-free system, suggesting that one or more metabolites of TCAN were responsible for the DNA adduct formation. ost of the radioactivity (50-80%) associated with globin obtained from either in vivo labeling or by incubation of [14C]-TCAN with whole blood could be released from the globin by the treatment with concentrated ammonium hydroxide.