The survival of cytochalasin‐induced polykaryons following exposure to cytotoxic agents.

Abstract

Using CHO-K1, HeLa S3 and two Walker lines (WR and WS) differentially sensitive to cis-diamminedichloroplatinum(II) (cisplatin), the survival after exposure to cisplatin, mitomycin C, vinblastine, vincristine or cytosine arabinoside has been determined either of clonogens or of cells rendered polyploid by post-exposure incubation in the presence of cytochalasin B (CB). It is suggested that the inhibition of cytokinesis by CB permits an assessment to be made of the fraction of damage whose expression is cell division-related, possibly including that resulting from a loss or malsegregation of genetic material. It was found that the response of polykaryons in comparison to clonogens was both agent- and cell line-dependent. After cisplatin exposure, polykaryon survival (defined as the ability to accumulate at least 16C DNA) declined exponentially with dose and was qualitatively, and to some extent quantitatively, similar to that observed previously after irradiation. In HeLa S3, giant cells induced by 10-20Gy irradiation in the absence of CB exhibited a radiation dose-dependent reduction in the relative frequency of highly polyploid cells which was similar to that observed in CB-induced polykaryons.

Prediction of the Initial Slope of the Acute Clonogenic Survival Curve by the Post-irradiation Behaviour of Cytochalasin-induced Polykaryons

“…We have argued that this is consistent with the idea that the absence of cytokinesis confers partial protection in those cases where the loss of genetic material contributes to lethality (Court et al 1993). …”

“…CHO-K1 and HeLa S3 were maintained as previously described (Court et al 1993). V79-379A cells were grown in Dulbecco's modified Eagle's medium supplemented with 5% newborn calf serum plus 5% foetal calf serum (FCS), and the human colon carcinoma line WiDr was grown in minimum essential medium containing 10% FCS.…”

“…We have previously described a flow cytometric technique for the measurement of the number of CB-induced polykaryons per culture having a given DNA content , and have demonstrated that the fraction of cells able to achieve a high DNA content (>, 16C) decreases with dose following exposure to cytotoxic agents (Court et al 1993). We have argued that the survival of polykaryon-forming units (PFUs) may be considered to be analogous to that of clonogens, since in both cases cell cycle activity is required, while the major known difference is the presence or absence of cytokinesis.…”

“…Using this technique, we have observed that in 199,5 Taylor & Francis Ltd. the case of cytotoxic drugs, the relationship between clonogen and PFU survival is complex, and is dependent upon both drug and cell line (Court et al 1993). In most cases, however, the survival of PFUs accumulating at least 16C DNA shows a reduced dose-response (interpreted as greater resistance) in comparison with clonogens.…”

Cell structure and cytokinesis alterations in multidrug-resistant Leishmania (Leishmania) amazonensis

“…Since the survival of drug-induced polykarions may be associated with an altered susceptibility to different compounds (Court et al 1993), these aberrant forms must be considered in MDR studies. Although the early vinblastine effects on Leishmania may be reversed, the MDR phenotype and the ultrastructural alterations produced by long-term treatment were stable.…”