Morales-Ramírez P, Vallarino-Kelly T
Departamento de Genética, Instituto Nacional de Investigaciones Nucleares, Apartado Postal 18-1027, Mexico, D.F., Mexico.
Mutat Res. 1999 Jun 1;427(1):31-8. doi: 10.1016/S0027-5107(99)00082-2.
The kinetics of micronucleated polychromatic erythrocytes (MN-PCE) induction by methylnitrosourea (MNU) was determined in mice with the purpose of discerning whether or not the kinetics reflects the mechanism of chromosome break induction. A very long latency period (LP) was observed which is not compatible with an agent that does not require metabolic activation or incorporation to DNA for acting, but this is consistent with the mechanism demonstrated earlier that MNU causes chromosome breaks throughout the repair of mismatches induced by the alkylation of bases in a previous division. This is also supported by the presence of two rates of MN-PCE induction with respect to dose, which suggests that MN-PCE are induced by two mechanisms, an efficient one induced with the lower dose, and another less efficient one induced with higher doses. A similar behavior was observed in the curve of LP vs. dose, the lower dose causes 8 h of LP and higher doses increase LP but not proportionally to dose. The lower dose did not cause a reduction in the proportion of polychromatic erythrocytes, suggesting that this dose did not produce an important cytotoxic effect that could explain the long LP.
为了确定甲基亚硝基脲（MNU）诱导小鼠微核多染性红细胞（MN-PCE）的动力学是否反映染色体断裂诱导机制，对其进行了测定。观察到一个非常长的潜伏期（LP），这与一种不需要代谢活化或整合到DNA中就能起作用的试剂不相符，但这与早期证明的机制一致，即MNU在先前分裂中碱基烷基化诱导的错配修复过程中导致染色体断裂。这也得到了MN-PCE诱导率与剂量相关的两种速率的支持，这表明MN-PCE是由两种机制诱导的，一种是低剂量诱导的高效机制，另一种是高剂量诱导的低效机制。在LP与剂量的曲线中观察到类似的行为，较低剂量导致8小时的LP，较高剂量增加LP，但与剂量不成比例。较低剂量并未导致多染性红细胞比例降低，这表明该剂量并未产生可解释长LP的重要细胞毒性作用。
