A Two-compartment Model of Micronucleus Formation in Erythrocytes and its Application to Mouse Bone Marrow. I. Rectangularly Transient Action of Clastogen in Stationary Conditions

The micronucleation process of mouse erythrocytes caused by a clastogen has been described by means of a two-compartment model in which the bone marrow pool of polychromatic erthrocytes (PCE) and of normochromatic erythrocytes (NCE) are considered to be the compartments. The kinetic processes involved in this system and its rates (in parentheses) are: the generation of PCE (kg), the micronucleation of erythrocytes (kMN), the maturation of PCE to NCE (km) and the removal of NCE (kout) and of micronucleated NCE (kMNout). It is assumed that kMN = kinjkg, where kinj is an injury factor which may depend on the clastogen concentration. The model has been applied to the data published by Hayashi et al. (1984) for the frequency of micronucleated PCE under the assumptions that the clastogen "dose" was constant during a period T and the PCE generation was steady and unperturbed by the clastogen. For the three chemicals used—mytomycin C (MMC), 6-mercaptopurine (6-MP) and 1-β-D-arabinofuranosylcytosine (Ara-C)—the following parameters were obtained: kinj = 5·4%, km = 0·069 hr-1, T = 24 hr (MMC); kinj = 7·0%, km = 0·075 hr-1, T = 24 hr (6-MP) and kinj = 4·3%, km = 0·083 hr-1T = 22 hr (Ara-C). The Ara-C data set best fitted the two-compartment model under the assumptions stated above. It has been suggested that the deviations from the theoretical predictions may be due to varying with time clastogen concentration and non-steady PCE generation.