TY - JOUR
T1 - Comparative metabolism and DNA binding of 1-, 2-, and 4-nitropyrene in rats
AU - Chae, Y. H.
AU - Upadhyaya, P.
AU - Ji, B. Y.
AU - Fu, P. P.
AU - El-Bayoumy, K.
N1 - Funding Information:
We thank the staff of the Research Animal Facility for handling animals. We appreciate the editorial assistance of Mrs. Ilse Hoffmann. This study was supported by the National Cancer Institute grant No. CA 35519 (K.ELB). This paper was presented at the Sixth International Conference on Carcinogenic and Mutagenic N-Substituted Compounds held in Monterey, CA (USA), November 4–8, 1995.
PY - 1997/5/12
Y1 - 1997/5/12
N2 - The metabolism and DNA binding studies of mono-NP isomers under identical conditions were conducted, as an initial investigation, in order to provide an understanding for the higher carcinogenic activity of 4-NP in the rat mammary gland. Urinary and fecal excretion patterns of 4-NP and 1-NP 24 h following administration to female CD rats tip; 24 mg/kg body weight; 1.55 mCi/rat) were similar but higher than those of 2-NP. The identified metabolites were formed via nitroreduction and ring oxidation pathways. Neither the excretion patterns nor the nature of the metabolites readily explained why the mammary tumorigenic activity of these three isomers varied. Although overall levels of mono-NP bound to liver DNA did not account for the observed differences in the biological activity, further HPLC analysis of the liver DNA hydrolysates showed that only 4-NP had yielded putative multiple DNA adducts; none were detected in the case of 1-NP and 2-NP. 1-, 2-, and 4-NP were found to bind to mammary DNA at levels of 0.6, 0.3, and 2.1 pmol/mg DNA, respectively. The structure of DNA adducts in the mammary gland and in the liver of female CD rats following the i.p. administration of 4-NP has not been identified. Collectively, the results of this preliminary study indicate that the difference in levels of DNA binding in the mammary gland in vivo may reflect why 4-NP has higher carcinogenic activity.
AB - The metabolism and DNA binding studies of mono-NP isomers under identical conditions were conducted, as an initial investigation, in order to provide an understanding for the higher carcinogenic activity of 4-NP in the rat mammary gland. Urinary and fecal excretion patterns of 4-NP and 1-NP 24 h following administration to female CD rats tip; 24 mg/kg body weight; 1.55 mCi/rat) were similar but higher than those of 2-NP. The identified metabolites were formed via nitroreduction and ring oxidation pathways. Neither the excretion patterns nor the nature of the metabolites readily explained why the mammary tumorigenic activity of these three isomers varied. Although overall levels of mono-NP bound to liver DNA did not account for the observed differences in the biological activity, further HPLC analysis of the liver DNA hydrolysates showed that only 4-NP had yielded putative multiple DNA adducts; none were detected in the case of 1-NP and 2-NP. 1-, 2-, and 4-NP were found to bind to mammary DNA at levels of 0.6, 0.3, and 2.1 pmol/mg DNA, respectively. The structure of DNA adducts in the mammary gland and in the liver of female CD rats following the i.p. administration of 4-NP has not been identified. Collectively, the results of this preliminary study indicate that the difference in levels of DNA binding in the mammary gland in vivo may reflect why 4-NP has higher carcinogenic activity.
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U2 - 10.1016/S0027-5107(97)00021-3
DO - 10.1016/S0027-5107(97)00021-3
M3 - Article
C2 - 9202734
AN - SCOPUS:0030925918
SN - 0027-5107
VL - 376
SP - 21
EP - 28
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -