Tan D X, Pöeggeler B, Reiter R J, Chen L D, Chen S, Manchester L C, Barlow-Walden L R
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
Cancer Lett. 1993 Jun 15;70(1-2):65-71. doi: 10.1016/0304-3835(93)90076-l.
Melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in a dose-dependent manner. Total DNA-adduct formation after in vivo administration of 300 mg/kg safrole measured by 32P-postlabeling analysis of carcinogen-modified DNA in rat liver was 36,751 +/- 2290 counts/min/10 micrograms DNA. Coadministration of 300 mg/kg safrole with either 0.2 mg/kg (low dose) or 0.4 mg/kg (high dose) melatonin reduced DNA-adduct formation induced by safrole to 22,182 +/- 987 counts/min/10 micrograms DNA and 462 +/- 283 counts/min/10 micrograms DNA, respectively. Circulating melatonin concentrations at the termination of the study in safrole, low melatonin and high melatonin groups were 50 +/- 8, 3140 +/- 430 and 10,040 +/- 2610 pg/ml serum, respectively. The results suggest that melatonin protects against safrole associated DNA damage.
褪黑素以剂量依赖的方式抑制化学致癌物黄樟素诱导的DNA加合物形成。通过对大鼠肝脏中致癌物修饰的DNA进行³²P后标记分析,体内给予300mg/kg黄樟素后,总的DNA加合物形成量为36,751±2290计数/分钟/10μg DNA。将300mg/kg黄樟素与0.2mg/kg(低剂量)或0.4mg/kg(高剂量)褪黑素共同给药后,黄樟素诱导的DNA加合物形成量分别降至22,182±987计数/分钟/10μg DNA和462±283计数/分钟/10μg DNA。在研究结束时,黄樟素组、低剂量褪黑素组和高剂量褪黑素组血清中循环褪黑素浓度分别为50±8、3140±430和10,040±2610pg/ml。结果表明,褪黑素可预防与黄樟素相关的DNA损伤。