l) Nitrated polycyclic aromatic hydrocarbons(Nitroarenes) are of concern since they may become widely spread in the environment. These compounds have been identified as potent bacterial mutagens. 2) While the mechanism of action of these compounds in bacterial systems is fairly well documented the evidence for mechanism of action and potency in mammalian systems is less well documented and inconsistent. 3) We have shown that 2,4,7trinitro-9 fluorenone (TNF) is highly genotoxic to 2 rodent cell lines and to a human cell line. In all three cell lines sister chromatid exchanges (SCEs) are induced using low concentrations of TNF. Inhibition of DNA synthesis is likewise achieved with similar low concentrations of TNF. 4) We now wish to extend this investigation to examine the potency of TNF in inducing mutations in both chinese hamster ovary cells and in the human teratocarcinoma cell line at the hypoxanthine guanine phosphoribosyl transferase locus (HGPRT). The nature of the mutations induced by TNF will be examined using a cDNA probe to the HGPRT gene. Genomic DNA endonuclease fragments of control and mutant cells will be examined of Southern blots to search for deletion/translocation mutants. Total RNA extracts from control and mutant cells will likewise be analyzed on Northern gels for altered transcription of the HGPRT gene.
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