DNA adduct formation in primary rabbit tracheal epithelial cells following treatment with 1,8-dinitropyrene and its partially reduced derivative, 1-nitro-8-nitrosopyrene.
Formation of DNA adducts, following treatment of primary rabbit tracheal epithelial cells (RTEC) with 1,8-dinitropyrene (1,8-DNP) and its partially reduced derivative, 1-nitro-8-nitrosopyrene (1,8-NONO2), was examined using the 32P-post-labelling technique. Treatment of aerobic cells with 1,8-DNP or 1,8-NONO2 produced qualitatively similar results. Cochromatography showed that the major adduct observed corresponded to the major adduct seen following treatment of poly(dG.dC) with N-hydroxyl-1-amino-8-nitropyrene, generated from 1,8-NONO2. A minor adduct migrated to the same area on the TLC plate as the major compound observed following a similar treatment with poly(dA.dT). Relative adduct labelling (RAL) values were consistently an order of magnitude higher with 1,8-NONO2 than with 1,8-DNP, suggesting that reduction of a nitro group of 1,8-DNP to a nitroso group may be a rate-limiting step in the cells. In studies on the formation and persistence of the 1,8-NONO2 adduct in RTEC maximum binding was observed at 1 h. Fifteen hours later the RAL value was less than 15% of this maximum level.
Norman
C A
CA
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
Lambert
I B
IB
Davison
L M
LM
Bryant
D W
DW
McCalla
D R
DR
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D007700:Kinetics; D009603:Nitroso Compounds / Q000032:analysis*; D010761:Phosphorus Radioisotopes; D011721:Pyrenes / Q000032:analysis* / Q000378:metabolism*; D011817:Rabbits; D011865:Radioisotope Dilution Technique; D014132:Trachea / Q000378:metabolism*
D002273:Carcinogens; D009603:Nitroso Compounds; D010761:Phosphorus Radioisotopes; D011721:Pyrenes; C047861:1-nitro-8-nitrosopyrene; C033310:1,8-dinitropyrene; D004247:DNA; C037413:1,3-dinitropyrene