PMID- 1306295 OWN - NLM STAT- MEDLINE DCOM- 19930805 LR - 20190727 IS - 0040-8727 (Print) IS - 0040-8727 (Linking) VI - 168 IP - 2 DP - 1992 Oct TI - Role of intestinal microflora in metabolism of glutathione conjugates of 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide. PG - 119-22 AB - DNA adduct formation in the liver of B6C3F1 mice after administration of 1-nitropyrene (1-NP) was shown by the 32P-postlabeling technique. The major adduct was not N-(deoxyguanosin-8-yl)-1-aminopyrene, which was easily formed in in vitro nitroreduction of 1-NP in the presence of DNA, but the major spots migrated to the same position as the in vitro DNA adduct spots of K-region epoxides of 1-NP (1-NP 4,5- and 9,10-oxide). 1-NP oxides formed by the oxidative activation of 1-NP in the liver were excreted into the bile as detoxified glutathione conjugates which were changed to cysteine conjugates in the upper intestinal tract. The cysteine conjugates were degraded by cysteine conjugate beta-lyase (beta-lyase) of intestinal microflora in the lower intestinal tract. The mutagenicity of cysteine conjugates of 1-NP oxides for Salmonella typhimurium was enhanced by addition of beta-lyase and was decreased by addition of aminooxyacetic acid, a beta-lyase inhibitor. The in vitro binding of the cysteine conjugates to calf thymus DNA was increased by addition of beta-lyase and xanthine oxidase. We administered glutathione conjugates of 1-NP oxides to two groups of mice that had been treated with antibiotics or saline by gavage and analyzed the DNA adducts in the lower intestinal mucosa. The specific DNA adducts were detected in the saline-treated group but not in the antibiotics-treated group. These results suggest that intestinal microflora play an important role in activation of glutathione conjugates of 1-NP oxides. FAU - Kinouchi, T AU - Kinouchi T AD - Department of Bacteriology, School of Medicine, University of Tokushima, Japan. FAU - Kataoka, K AU - Kataoka K FAU - Miyanishi, K AU - Miyanishi K FAU - Akimoto, S AU - Akimoto S FAU - Ohnishi, Y AU - Ohnishi Y LA - eng PT - Journal Article PL - Japan TA - Tohoku J Exp Med JT - The Tohoku journal of experimental medicine JID - 0417355 RN - 0 (Pyrenes) RN - 105596-42-7 (1-nitropyrene-4,5-oxide) RN - 105596-43-8 (1-nitropyrene-9,10-oxide) RN - 9007-49-2 (DNA) RN - EC 4.- (Lyases) RN - GAN16C9B8O (Glutathione) RN - TD1665I8Q4 (1-nitropyrene) SB - IM MH - Animals MH - Bacteria/enzymology/*metabolism MH - DNA/metabolism MH - Glutathione/*chemistry/metabolism MH - Intestines/*microbiology MH - Liver/*metabolism MH - Lyases/metabolism MH - Mice MH - Mice, Inbred Strains MH - Pyrenes/*chemistry/*metabolism EDAT- 1992/10/01 00:00 MHDA- 1992/10/01 00:01 CRDT- 1992/10/01 00:00 PHST- 1992/10/01 00:00 [pubmed] PHST- 1992/10/01 00:01 [medline] PHST- 1992/10/01 00:00 [entrez] AID - 10.1620/tjem.168.119 [doi] PST - ppublish SO - Tohoku J Exp Med. 1992 Oct;168(2):119-22. doi: 10.1620/tjem.168.119.