DETECTION OF ONCOGENE ALTERATIONS IN MICE INDUCED BY CHLOROPRENE

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Summary of Work: A high frequency 80% of K-ras mutations were detected in chloroprene-induced lung neoplasms than in spontaneous lung neoplasms (30%). Similarly, a high frequency (100%) of K- and H- ras codon 61 CTA mutations was identified in HG neoplasm, compared to a frequency of 56% in spontaneous HG neoplasms. The predominant mutation in both lung and HG neoplasms was an A to T transversion at K-ras codon 61; a mutation which has never been detected in spontaneous lung tumors of B6C3F, Mice, and detected in only 7% of spontaneous HG neoplasms. The tumor endpoint relevant to human exposure in this study was the lung where high numbers of A to T transversions were detected, however, our study also clearly showed that organ systems unique to the mouse such as the Harderian gland, provide data similar to that in the lung about chemical specific K-ras codon 61 CTA mutations and potential mechanisms of carcinognesis. This data was presented at the NTP and about potential mechansms of carcinogenesis. This data were presented at the NTP peer review in December 1996. The manuscript is prepared.