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 provide data 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 in press. Chloroprene induced forestomach neoplasms are being evaluated for genetic alterations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021184-06
Application #
6106583
Study Section
Special Emphasis Panel (LEP)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code