Metabolism and DNA binding of 1-nitropyrene and 1-nitrosopyrene in newborn mice.

Abstract

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)

• Authors: K el-Bayoumy, G H Shiue, S S Hecht
• Journal: Chemical research in toxicology (Chem Res Toxicol) 1988 Jul-Aug Vol. 1 Issue 4 Pg. 243-7 ISSN: 0893-228X [Print] United States
• PMID: 2979739 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carbon Radioisotopes
• Carcinogens
• Pyrenes
• Tritium
• 1-nitrosopyrene
• DNA
• 1-nitropyrene

Topics

• Animals
• Animals, Newborn
• Carbon Radioisotopes
• Carcinogens (metabolism)
• DNA (metabolism)
• Liver (metabolism)
• Mice
• Mice, Inbred ICR
• Pyrenes (metabolism)
• Radioisotope Dilution Technique
• Tritium