Balansky R, Adomat H, Bryson L
Institute of Hygiene and Preventive Medicine, University of Genoa, Italy.
Biol Trace Elem Res. 1994 Jul;42(1):53-61. doi: 10.1007/BF02990488.
The clastogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Chinese hamster ovary (CHO) cells and its modulation by Na2SeO3 and caffeine were studied by metaphase analysis of chromosome aberrations (CA) as well as by measuring the formation and repair of single-strand (ss) DNA breaks employing hydroxylapatite chromatography. Treatment of CHO cells with MNNG (1.25 or 2.5 x 10-5M) for 3 h caused CA in 11 and 19% of metaphases scored, respectively. Pretreatment of cells with Na2SeO3 (1-5 micrograms/mL) or caffeine (0.2-2.0 mg/mL) for 2 h resulted in a 2-3.5-fold increase of CA frequency. Addition of both modulators during the mutagen exposure tended to cause a slight inhibition of clastogenic activity of MNNG (1.25 x 10(-5) M) or had no effect on CA number when MNNG was used at a concentration of 2.5 x 10(-5) M). Posttreatment of CHO cells with Na2SeO3 for 20 h after MNNG was ineffective in influencing the number of metaphases with CA, whereas, at these conditions, caffeine enhanced up to 6-7-fold the clastogenic activity of MNNG. Addition of both modulators during the whole experiment, 2 h pretreatment included, resulted in a further significant increase of CA frequency up to the total pulverization of chromosomes in all metaphases scored. The coclastogenic effect of caffeine was greater in this case. The enhancement of chromosome-damaging activity of MNNG by selenite and caffeine was better expressed when this carcinogen was applied at the higher concentration used. An additive coclastogenic effect was observed in CHO cells treated simultaneously with Na2SeO3 and caffeine plus MNNG.(ABSTRACT TRUNCATED AT 250 WORDS)
通过染色体畸变（CA）的中期分析以及采用羟基磷灰石色谱法测量单链（ss）DNA断裂的形成和修复，研究了N-甲基-N'-硝基-N-亚硝基胍（MNNG）对中国仓鼠卵巢（CHO）细胞的致断裂作用及其受亚硒酸钠和咖啡因的调节情况。用MNNG（1.25或2.5×10⁻⁵M）处理CHO细胞3小时，分别导致在计分中期相中11%和19%出现CA。用亚硒酸钠（1 - 5微克/毫升）或咖啡因（0.2 - 2.0毫克/毫升）预处理细胞2小时，导致CA频率增加2 - 3.5倍。在诱变剂暴露期间添加两种调节剂，往往会对MNNG（1.25×10⁻⁵M）的致断裂活性产生轻微抑制，或者当MNNG浓度为2.5×10⁻⁵M时对CA数量没有影响。MNNG处理后用亚硒酸钠对CHO细胞后处理20小时，对出现CA的中期相数量没有影响，而在这些条件下，咖啡因使MNNG的致断裂活性增强高达6 - 7倍。在整个实验期间（包括2小时预处理）添加两种调节剂，导致CA频率进一步显著增加，直至在所有计分中期相中染色体完全粉碎。在这种情况下，咖啡因的共断裂作用更大。当使用较高浓度的这种致癌物时，亚硒酸盐和咖啡因对MNNG染色体损伤活性的增强作用表现得更明显。在同时用亚硒酸钠、咖啡因加MNNG处理的CHO细胞中观察到相加的共断裂作用。（摘要截断于250字）
