Induction of long-lived chromosome damage, as manifested by sister-chromatid exchange, in lymphocytes of animals exposed to mitomycin-C.
The cytogenetic effects of repeated vs. acute exposure to a chemical mutagen--carcinogen were determined with an in vivo system in which chemicals injected into rabbits induce sister-chromatid exchanges (SCEs). SCE induction can be monitored when the animal's peripheral lymphocytes are cultured in the presence of bromodeoxyuridine (BrdUrd) and then scored for SCE frequency. Mitomycin-C (MMC), 0.5 mg/kg, was injected intraperitoneally once a week for 8 weeks. This treatment initially induced small increases in SCE frequency within one day of injection, followed by a return to control levels within 1 week. After the 4th injection, however, the frequency failed to return to normal. After the 5th injection, however it showed a 4-fold increase over the control which was sustained for the remaining 3 weeks of treatment and for an additional 2 weeks thereafter. The frequency then dropped to twice the control value and remained at this level for more than 4 months. All of the high SCE values after the first 4 weeks were due in part to the appearance and persistence of a population of cells with high SCE frequencies. Exposure to the same total dose given as a single injection resulted in a transient elevation in the SCE frequency and a subsequent return to lower values, with no evidence of a delayed effect such as the increase observed after 4 weeks in repeatedly exposed animals. Overall, repeated exposure is at least as effective as acute exposure in eliciting long-lived SCEs in vivo.