Comparison of DNA alkylation, fragmentation, and repair in maternal and fetal tissues of pregnant rats treated with a single dose of ethyl methanesulfonate, ethyl-N-nitrosourea, N-nitrosodiethylamine, and methyl-N-nitrosourea.
The occurrence and persistence of DNA damage, as detected by the alkaline elution technique, have been studied in some tissues of both fetal and adult Sprague-Dawley rats (18th day of gestation) after administration of a single equimolar dose (0.5 mmol/kg) of ethyl methanesulfonate (EMS), N-ethyl-N-nitrosourea (ENU), N-nitrosodiethylamine (NDEA), and N-methyl-N-nitrosourea (MNU). EMS, ENU, and MNU, injected intravenously, produced a statistically significant increase of DNA elution rate, which is considered indicative of DNA fragmentation, in both maternal and fetal liver, kidney, and brain. NDEA, introduced by gastric gavage, induced DNA breaks in both liver and kidney of dams, but only in the liver of fetuses. The frequency of DNA lesions was found to vary with the four alkylating agents and in the three organs tested, to exhibit a different time course, and usually to be higher in maternal than in fetal tissues. Results provided by the concomitant determination of DNA binding levels demonstrated a satisfactory correlation with the amounts of DNA fragmentation. In contrast, the values of both these parameters did not show any positive correlation with the different susceptibility of the three organs to tumor induction. In conclusion, these findings suggest that when a compound is not available in radiolabeled form, measurement of DNA fragmentation may represent a useful alternative to the determination of DNA binding level in order to obtain information on the distribution of its reactive species in maternal and fetal tissues.
Robbiano
L
L
Institute of Pharmacology, University of Genoa, Italy.
Parodi
A
A
Venturelli
S
S
Brambilla
G
G
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens; D002845:Chromatography / Q000379:methods; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000187:drug effects*; D009603:Nitroso Compounds / Q000633:toxicity; D009928:Organ Specificity; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000477:Alkylating Agents; D002273:Carcinogens; D009603:Nitroso Compounds; D005020:Ethyl Methanesulfonate