Int. J. Mol. Sci. 2002, 3(9), 1019-1026; doi:10.3390/i3091019
Article

Detection of Riddelliine-Derived DNA Adducts in Blood of Rats Fed Riddelliine

1, 1, 2, 1 and 1,* email
Received: 7 June 2002; Accepted: 15 August 2002 / Published: 30 September 2002
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: We have previously shown that riddelliine, a naturally occurring genotoxic pyrrolizidine alkaloid, induces liver tumors in rats and mice through a genotoxic mechanism mediated by the formation of a set of eight 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine ( DHP)-derived DNA adducts. In this study we report the formation of these DHP-derived DNA adducts in blood DNA of rats fed riddelliine. In an adduct formation and removal experiment, male and female F344 rats (8 weeks of age) were administered riddelliine by gavage at a single dose of 10.0 mg/kg body weight in 0.1 M phosphate buffer. At 8, 24, 48, and 168 hrs after dosing, the levels of DHP-derived DNA adduct in blood and liver were determined by 32P-postlabeling/HPLC. Maximum DNA adduct formation occurred at 48 hr after treatment. From 48 to 168 hours, the adduct levels in female rat blood were 4-fold greater than those in male rats. In a dose response experiment, female rats were gavaged 0.1 and 1.0 mg/kg doses of riddelliine for three consecutive days and the DHPderived DNA adducts in blood DNA were assayed. The levels of the DHP-derived DNA adducts in blood of rats receiving 0.1 and 1.0 mg/kg doses were 12.9 and 51.8 adducts/107 nucleotides. These results suggest that: (i) leucocyte DNA can bind with DHP to form a set of DHP-derived DNA adducts generated in liver; (ii) DHP-derived DNA adducts in blood can serve as a potential non-invasive biomarkers for assessing the exposure to riddelliine.
Keywords: Pyrrolizidine alkaloids; riddelliine; dehydroretronecine; 32P-postlabeling/HPLC; rat blood DNA adducts
PDF Full-text Download PDF Full-Text [202 KB, uploaded 19 June 2014 00:02 CEST]

Export to BibTeX |
EndNote


MDPI and ACS Style

Yan, J.; Nichols, J.; Yang, Y.-C.; Fu, P.P.; Chou, M.W. Detection of Riddelliine-Derived DNA Adducts in Blood of Rats Fed Riddelliine. Int. J. Mol. Sci. 2002, 3, 1019-1026.

AMA Style

Yan J, Nichols J, Yang Y-C, Fu PP, Chou MW. Detection of Riddelliine-Derived DNA Adducts in Blood of Rats Fed Riddelliine. International Journal of Molecular Sciences. 2002; 3(9):1019-1026.

Chicago/Turabian Style

Yan, Jian; Nichols, Jasyl; Yang, Ya-Cheng; Fu, Peter P.; Chou, Ming W. 2002. "Detection of Riddelliine-Derived DNA Adducts in Blood of Rats Fed Riddelliine." Int. J. Mol. Sci. 3, no. 9: 1019-1026.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert