Oxidatively damaged DNA induced by humic acid and arsenic in maternal and neonatal mice.
We measured the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), a useful biomarker of oxidative injury, in liver (or urine) of maternal mice and their offspring, that were treated with humic acid (HA) and arsenic (As) alone, or their combination during pregnancy. A highly sensitive and specific isotope-dilution LC-MS/MS method was used for 8-oxodGuo quantification. Total arsenic accumulated in the offspring was also measured using ICP-MS. This study demonstrated, for the first time in an animal model, that HA alone treatment led to a significant increase of 8-oxodGuo levels both in liver and urine of maternal mice. No enhanced effect was observed when HA was combined with As, compared with the As alone treatment. With regard to the associated offspring, elevated levels of 8-oxodGuo and total arsenic were observed in offspring only when mother mice were treated with As and its combination with HA, but not for the HA-treated alone. It was worthy to note that the offspring from maternal combined treatment with HA and As had a significantly lower 8-oxodGuo than those of maternal treatment with As alone. This could be explained by that part of As formed complexes with HA and these macromolecules of HA-As complexes may not readily cross the placenta to the fetus, as evidenced by the lower accumulated total As observed in the offspring livers. Overall, it seems that HA may be detrimental to the maternal mice, but in the meantime it can be beneficial to the offspring by reducing free As.
Hu
Chiung-Wen
CW
Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan.
Yen
Cheng-Chieh
CC
Huang
Yeou-Lih
YL
Pan
Chih-Hong
CH
Lu
Fung-Jou
FJ
Chao
Mu-Rong
MR
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001151:Arsenic / Q000032:analysis / Q000633:toxicity*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000652:urine; D005260:Female; D006812:Humic Substances / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal
D006812:Humic Substances; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D001151:Arsenic