Different onsets of oxidative damage to DNA and lipids in bone marrow and liver in rats given total body irradiation.
We examined time-dependent changes in antioxidant vitamins and oxidative damage to DNA and lipids in the bone marrow, liver, and plasma of rats given total body irradiation (TBI) with X-rays at 3 Gy. The oxidative damage to DNA and lipids was evaluated by measuring increases of 8-hydroxydeoxyguanosine (8OHdG) in DNA and 4-hydroxy-2-nonenal (HNE), respectively. After the TBI, marked increases in 8OHdG and HNE were detected at 3 to 5 h in the bone marrow, while gradual increases in these parameters were detected after a few days in the liver. These changes in 8OHdG and HNE were well correlated within each tissue. In the bone marrow, levels of both vitamin C and vitamin E were decreased by the TBI; however, the changes in vitamin C were earlier and greater than those in vitamin E. In the liver, the level of vitamin C did not decrease, but that of vitamin E decreased due to the TBI. Changes in HNE, vitamin C, and vitamin E in the plasma were similar to those in the liver. Within each tissue, the time of decrease in antioxidants was almost the same as that of the increase in oxidative damage. An increase in total iron due to the TBI was also detected in these tissues. In particular, the total iron in the bone marrow was markedly increased at a few hours after the TBI, with a slight increase in transferrin and no increase in ferritin. Exposure studies performed on cells or isolated DNA showed that an increase in 8OHdG was detected immediately after irradiation at more than 100 Gy in bone marrow cells and at less than 10 Gy in isolated DNA, suggesting that an increase in 8OHdG is undetectable even in bone marrow immediately after the TBI at 3 Gy. These results indicate that the onset of oxidative damage to DNA and lipids was delayed after TBI at 3 Gy, that it was quite different in the bone marrow and the liver, and that an increase in iron and decrease in antioxidant vitamins were involved in the mechanism of oxidative damage.
Umegaki
K
K
Department of Food Science Research for Health, The National Institute of Health and Nutrition, Tokyo, Japan. umegaki@nih.go.jp
Sugisawa
A
A
Shin
S J
SJ
Yamada
K
K
Sano
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000819:agonists; D000818:Animals; D001205:Ascorbic Acid / Q000528:radiation effects; D001853:Bone Marrow / Q000528:radiation effects*; D004247:DNA / Q000528:radiation effects*; D003849:Deoxyguanosine / Q000819:agonists / Q000031:analogs & derivatives*; D005293:Ferritins / Q000528:radiation effects; D007501:Iron / Q000528:radiation effects; D008055:Lipids / Q000528:radiation effects*; D008099:Liver / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D009929:Organ Size / Q000528:radiation effects; D018384:Oxidative Stress / Q000502:physiology; D011829:Radiation Dosage; D051381:Rats; D017208:Rats, Wistar; D014168:Transferrin / Q000528:radiation effects; D014810:Vitamin E / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D000447:Aldehydes; D008055:Lipids; D014168:Transferrin; D014810:Vitamin E; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D005293:Ferritins; D007501:Iron; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal; D001205:Ascorbic Acid