Relationship between the kinetics of micronuclei induction and the mechanism of chromosome break formation by methylnitrosourea in mice in vivo

Abstract

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.