Pharmacokinetic parameters determined from the clastogenic activity of ethylnitrosourea and dimethylnitrosamine in mice in vivo.
The latency period (LP) and the time of effective activity (TEA) of ethylnitrosourea (ENU) and dimethylnitrosamine (DMN) were inferred by comparing their kinetics of micronucleated polychromatic erythrocytes (MN-PCE) formation with the kinetics induced by radiation. The results indicate that LP and TEA vary between ENU and DMN. For ENU, these parameters are very similar to radiation indicating a rapid distribution, reaction and elimination. DMN presents a very long LP which agrees with the requirement of mutagen activation. The kinetics of MN-PCE production caused by DMN showed two peaks; this could be due to the presence of two different metabolites, two types of lesions in DNA or two mechanisms of MN-PCE formation. These hypotheses do not exclude each other. The data presented here support the conclusion that the comparison of MN-PCE-formation kinetics induced by chemical agents with that caused by radiation permits one to estimate the LP and the TEA, and provide information on the possible mechanism of action of chemical mutagens.
Morales-Ramírez
P
P
Departamento de Genética, Instituto Nacional de Investigaciones Nucleares, México, D.F., Mexico.
Vallarino-Kelly
T
T
D000818:Animals; D002869:Chromosome Aberrations; D004128:Dimethylnitrosamine / Q000493:pharmacokinetics*; D004912:Erythrocytes / Q000378:metabolism* / Q000528:radiation effects; D005038:Ethylnitrosourea / Q000493:pharmacokinetics*; D005720:Gamma Rays; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048629:Micronuclei, Chromosome-Defective / Q000378:metabolism* / Q000528:radiation effects; D009153:Mutagens / Q000493:pharmacokinetics*
D009153:Mutagens; D004128:Dimethylnitrosamine; D005038:Ethylnitrosourea