||N-Nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone Induced Morphological Transformation of C3H/10T1/2CL8 Cells Expressing Human Cytochrome P450 2A6.
Nesnow, S. ;
Beck, S. ;
Rosenblum, S. ;
Lasley, J. ;
Tiano, H. F. ;
||Environmental Health Research and Testing, Inc., Research Triangle Park, NC. ;National Inst. of Environmental Health Sciences, Research Triangle Park, NC. Environmental Carcinogenesis and Mutagenesis Branch. ;Gentest Corp., Woburn, MA.;Health Effects Research Lab., Research Triangle Park, NC.
||EPA-68-D1-0148 ;EPA-Y01-ES-00186; EPA/600/J-94/417;
Transformed cell line ;
C3H inbred mice ;
Genetic vectors ;
Cell division ;
Cytochrome P450 2A6 ;
||Some EPA libraries have a fiche copy filed under the call number shown.
||Transfection of specific genes into cells capable of expressing chemically induced morphological cell transformation provides a valuable approach to study the mechanisms of action of carcinogens. A human cytochrome P450 isozyme, CYP2A6, has been successfully expressed from a retroviral vector in transformable C3H/10T1/2(10T1/2) mouse embryo fibroblasts and these resulting 10T1/2 clones were evaluated for the cytotoxic and transforming activites of two nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosodiethylamine (DEN). 10T1/2 clone 29 cells, which expressed high levels of CYP2A6 activity, were responsive to the cytotoxic and morphological transforming effects of DEN or NNK on a concentration-related basis. In 10T1/2 clone 29 cells, DEN at 600 micrograms/ml decreased cell survival to 67%, and induced 0.5 type II & III foci/fish. NNK at 400 micrograms/ml administered to 10T1/2 cells and 10T1/2 clone 4 cells (infected with the vector but not expressing the CYP2A6 activity) were unresponsive. These results indicate that expression of a cDNA coding for cytochrome P450 in 10T1/2 cells can provide information about the role of the enzyme in the activities of chemical carcinogens and also increase the sensitivity of 10T1/2 cells to a larger number of classes of chemical carcinogens. (Copyright (c) 1994 Elsevier Science B.V.)
||Pub. in Mutation Research Letters, v324 n3 p93-102 Jul 94. Prepared in cooperation with National Inst. of Environmental Health Sciences, Research Triangle Park, NC. Environmental Carcinogenesis and Mutagenesis Branch. and Gentest Corp., Woburn, MA. Sponsored by Health Effects Research Lab., Research Triangle Park, NC.
||%AUT:M. /Hosokawa ;C. L. /Crespi ;R. /Langenbach
|NTIS Title Notes
||Reprint: N-Nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone Induced Morphological Transformation of C3H/10T1/2CL8 Cells Expressing Human Cytochrome P450 2A6.
||PC A03/MF A01