Effect of caffeine on the frequency of chromosome aberrations induced in vivo by triethylenemelamine (TEM) and adriamycin (ADR) in mice.

The effect of caffeine on the chromosomal aberrations induced in vivo by TEM and ADR was studied. BALB/c mice were treated intraperitoneally according to the schedule summarized in Table 1. Animals injected only with caffeine exhibited a significant increase in the frequency of gaps with the doses of 100 and 150 mg/kg and in the frequency of breaks with all the doses given. Treatments with TEM induced a significant increment of gaps, breaks and chromatid exchanges. ADR increased the frequency of gaps and breaks and induced centric fusions. Combined treatments with TEM plus caffeine evidenced the potentiating ability of the latter drug. Conversely, in mice injected with ADR and caffeine, only the frequency of centric fusions was increased. These results could be explained by assuming that: (1) the primary lesions induced by ADR are not repaired by post-replication mechanisms; (2) the binding of ADR to the DNA molecule inhibits the unscheduled DNA synthesis necessary to perform the reparation of damaged segments. On the other hand, the increased frequency of biarmed chromosomes in ADR-caffeine treatments probably results from the induction of chromosomal stickiness of the heterochromatin regions.