METABOLIC DIFFERENCES BETWEEN WHOLE-BLOOD AND ISOLATED LYMPHOCYTE-CULTURES FOR MICRONUCLEUS (MN) INDUCTION BY CYCLOPHOSPHAMIDE AND BENZO[A]PYRENE

In order to study the metabolic differences between whole blood and is olated lymphocyte cultures, two indirectly acting mutagens cyclophosph amide (CP) and benzo[a]pyrene (B[a]P) were assessed for their potentia l to induce micronuclei (MN) in the presence and absence of S9 microso mal fractions. In isolated lymphocyte cultures supplemented with S9, C P and B[a]P induced a statistically significant increase in MN which w as not observed in whole blood cultures. However, the direct-acting ag ent methyl methanesulphonate (which was used as a positive control) sh owed an increase in MN frequency in a dose-dependent manner in both cu lture methods. The effect of erythrocytes was then investigated by tre ating isolated lymphocyte cultures simultaneously with CP and S9 mix i n the presence of purified erythrocyte concentrate (PEC). A clear redu ction in the MN frequency was observed compared to the frequencies of MN induced in isolated lymphocyte cultures treated with CP and S9 mix in the absence of PEC. Thus, isolated lymphocyte cultures mag represen t a more sensitive test system for the evaluation of potential indirec t-acting mutagens. However, whole blood cultures may reflect the 'real life' situation more accurately as a consequence of the presence of e rythrocytes.