Metabolism and DNA binding of 1-nitropyrene and 1-nitrosopyrene in newborn mice.
This study was carried out in order to evaluate possible mechanisms responsible for tumor induction by 1-nitropyrene and to provide insights on the higher tumorigenicity of 1-nitrosopyrene than 1-nitropyrene in newborn mouse liver. The "ground mouse" technique was used to follow the development of the metabolism of 1-nitropyrene and 1-nitrosopyrene in newborn and infant mice in vivo. Equimolar doses of 1-nitropyrene and 1-nitrosopyrene were used as in the bioassay reported previously. The compounds were administered by ip injection (100 nmol, day 1; 200 nmol, day 8; 400 nmol, day 15). The ethyl acetate soluble metabolites of 1-nitropyrene were identified as 1-aminopyrene, trans-4,5-dihydro-4,5-dihydroxy-1-nitropyrene, 1-nitropyren-3-ol, 1-nitropyren-6-ol, and 1-nitropyren-8-ol on the basis of cochromatography with synthetic standards in two different HPLC systems. Nitroreduction of 1-nitropyrene to 1-aminopyrene was observed only in 1 day old mice. Ethyl acetate soluble metabolites of 1-nitrosopyrene were identified as 1-aminopyrene and 1-nitropyrene. The capacity of 1 day old mice to metabolize 1-nitropyrene and 1-nitrosopyrene exceeded those of 8 and 15 day old mice. The extent of nitroreduction of 1-nitrosopyrene exceeded that of 1-nitropyrene. A major DNA adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene, was identified and quantified in liver and in lung, 24 h after carcinogen treatment. The extents of formation of this adduct (pmol/mg of DNA, mean of two experiments) were as follows: 1-nitropyrene (liver, 4.1; lung, 1.2); 1-nitrosopyrene (liver, 30.4; lung, 6.3).(ABSTRACT TRUNCATED AT 250 WORDS)
el-Bayoumy
K
K
Section of Biological Chemistry, American Health Foundation, Valhalla, New York 10595.
Shiue
G H
GH
Hecht
S S
SS
D000818:Animals; D000831:Animals, Newborn; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D011721:Pyrenes / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D014316:Tritium
D002250:Carbon Radioisotopes; D002273:Carcinogens; D011721:Pyrenes; D014316:Tritium; C044707:1-nitrosopyrene; D004247:DNA; C032668:1-nitropyrene