Iron-induced oxidative DNA damage in rat sperm cells in vivo and in vitro

We investigated whether acute iron intoxication causes oxidative DNA damage , measured in terms of 7-hydro-8-oxo-2'-deoxyguanosine, 8-oxodG, in nuclear DNA in testes and epididymal sperm cells in vivo and in vitro in rats. In addition, we investigated levels of the modified nucleoside in liver and ki dney and measured its urinary excretion. Sperm cells were isolated from the epididymides and the testes cells were i solated after homogenisation. In vitro, the sperm and testes cells were inc ubated with increasing concentrations of FeCl2 ranging from 0 to 600 mu M. The median (range) levels of 8-oxodG/10(5) dG in the epididymal sperm cells increased from 0.48 (0.42-0.90) to 15.1 (11.4-17.6) (p < 0.05), whereas th e level rose from 0.63 (0.22-0.81) to 8.8 (4.5-11.6) (p < 0.05) at 0 and 60 0 mu M, respectively, in the testicular cells. In vivo groups of 7-8 rats received 0, 200 or 400 mg iron/kg as dextran i.p . After 24 h, epididymal sperm cells, testes, kidneys and liver were collec ted for analysis. Kidney and sperm DNA showed a significant increase in 8-o xodG in the iron-treated animals. The median (range) values of the 8-oxodG/ 105 dG in the epididymal sperm cells rose from 0.66 (0.38-1.09) to 1.12 (0. 84-5.88) (p < 0.05) at 0 and 400 mg iron/kg, respectively, whereas the valu es in the testes and liver showed no significant change. In the kidneys the 8-oxodG/10(5) dG median (range) values were 0.98 (0.73-1.24), 1.21 (1.13-1 .69) and 1.34 (1.12-1.66) after 0, 200 and 400 mg iron/kg, respectively (p < 0.05). The 8-oxodG-excretion rate was measured in 24 h urine before and after iron treatment. The rate of urinary 8-oxodG excretion increased from 129 (104-1 79) pmol/24 h before treatment to 147 (110-239) pmol/24 h after treatment i n the group receiving 400 mg iron/kg (p < 0.05). The results indicate that acute iron intoxication may increase oxidative da mage to sperm and kidney DNA.