-transparent.png){kind=logo}
Riddelliine is a representative naturally occurring genotoxic pyrrolizidine alkaloid. We have studied the mechanism by which riddelliine induces hepatocellular tumors in vivo. Metabolism of riddelliine by liver microsomes of F344 female rats generated riddelliine N-oxide and dehydroretronecine (DHR) as major metabolites. Metabolism was enhanced when liver microsomes from phenobarbital-treated rats were used. Metabolism in the presence of calf thymus DNA resulted in eight DNA adducts that were identical to those obtained from the reaction of DHR with calf thymus DNA. Two of these adducts were identified as DHR-modified 7-deoxyguanosin-N(2)-yl epimers (DHR-3'-dGMP); the other six were DHR-derived DNA adducts, but their structures were not characterized. A similar DNA adduct profile was detected in the livers of female F344 rats fed riddelliine, and a dose-response relationship was obtained for the level of the total (eight) DHR-derived DNA adducts and the level of the DHR-3'-dGMP adducts. These results suggest that riddelliine induces liver tumors in rats through a genotoxic mechanism and the eight DHR-derived DNA adducts are likely to contribute to liver tumor development.
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
August 2005,
Cancer letters,
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
April 2005,
International journal of environmental research and public health,
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
January 2003,
Chemical research in toxicology,
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
July 2018,
Chemical research in toxicology,
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
November 2007,
BMC bioinformatics,
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
September 2003,
Chemical research in toxicology,
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
May 2008,
Toxicology letters,
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
January 2006,
Cancer letters,
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
July 2002,
Toxicology and applied pharmacology,
Y C Yang, and
J Yan, and
D R Doerge, and
P C Chan, and
P P Fu, and
M W Chou
August 2012,
Drug metabolism and disposition: the biological fate of chemicals,
