Induction of hepatic DNA single strand breaks in rats by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Previous studies have demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces lipid peroxidation in hepatic and extrahepatic tissues. DNA single strand breaks as well as other forms of DNA damage are believed to occur in conjunction with lipid peroxidation. We have therefore examined the effect of TCDD on hepatic DNA single strand breaks. Ten days after the administration of 100 micrograms TCDD/kg to female rats, a 7.5-fold increase in the DNA elution constant (single strand breaks) occurred. Similar changes were observed in the content of thiobarbituric acid reactive substances (TBARS) in the nuclei as well as the NADPH-dependent production of TBARS. The accumulation of TBARS appeared to precede the accumulation of DNA single strand breaks. The tumor promoting effects of TCDD may be associated with the enhanced formation of DNA single strand breaks.
Wahba
Z Z
ZZ
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha 68105-1065.
Lawson
T A
TA
Stohs
S J
SJ
D000818:Animals; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D005609:Free Radicals; D008054:Lipid Peroxides / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D004277:DNA, Single-Stranded; D004147:Dioxins; D005609:Free Radicals; D008054:Lipid Peroxides; D000072317:Polychlorinated Dibenzodioxins; D010100:Oxygen