DNA modification and repair by 2-nitropropane is extensive in hepatocytes of rats compared to those of humans and mice.
Hepatocytes from rats, mice or humans were exposed to either 2-nitropropane or propane 2-nitronate and the extent of unscheduled DNA synthesis (UDS) was measured. At a concentration of 2-nitropropane (0.1 mM) that produced a marked induction of UDS in rat hepatocytes, a negative or minimal response was seen in hepatocytes from mice and humans. A 10-fold higher concentration of 2-nitropropane was required in mouse hepatocytes for an equivalent UDS response to that seen in rat-liver cells. All three species showed UDS after exposure of hepatocytes to propane 2-nitronate at 0.1 mM although the effect in human cells was variable. In rat hepatocytes the induction of UDS by 2-nitropropane was not inhibited by the antioxidant dimethyl sulphoxide (1%). In these cells, 2-nitropropane produced an electrochemically active modified deoxynucleoside, similar to that reported to be formed in livers of rats which had received 2-nitropropane in vivo. A smaller but significant production of this altered deoxynucleoside was found in mouse hepatocytes but not in human hepatocytes treated identically. The level of 8-oxo-7,8-dihydrode-oxyguanosine was not increased in hepatocytes from any of the three species exposed to 2-NP under the same conditions. It is suggested that the UDS caused by 2-nitropropane may be in response to damage other than that produced by oxygen radicals.
Davies
J E
JE
School of Biochemistry, University of Birmingham, Edgbaston, UK.
Mynett
K
K
Gescher
A
A
Chipman
J K
JK
D000328:Adult; D000818:Animals; D004247:DNA / Q000187:drug effects*; D004260:DNA Repair; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009595:Nitroparaffins / Q000633:toxicity*; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000633:toxicity*; D013045:Species Specificity
D009595:Nitroparaffins; D012997:Solvents; D004247:DNA; C016617:2-nitropropane; D011407:Propane; D004121:Dimethyl Sulfoxide