Record Display for the EPA National Library Catalog


Main Title N-Nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone Induced Morphological Transformation of C3H/10T1/2CL8 Cells Expressing Human Cytochrome P450 2A6.
Author Nesnow, S. ; Beck, S. ; Rosenblum, S. ; Lasley, J. ; Tiano, H. F. ;
CORP Author 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.
Publisher 1994
Year Published 1994
Report Number EPA-68-D1-0148 ;EPA-Y01-ES-00186; EPA/600/J-94/417;
Stock Number PB95-125290
Additional Subjects Diethylnitrosamine ; Transformed cell line ; C3H inbred mice ; Retroviridae ; Genetic vectors ; Cell division ; Benzo(a)pyrene ; Reprints ; Cytochrome P450 2A6 ; Butanone/4-(methylnitrosoamino)-1-(3-pyridyl)-1
Library Call Number Additional Info Location Last
NTIS  PB95-125290 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 14p
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.)