Resting cells in tumours present a major problem in cancer chemotherapy.
In the plateau phase of growth of the murine JB‐1 ascites tumour (i.e. 10 days after 2–5 × 106 cells i.p.) large fractions of non‐cycling cells with G1 and G2 DNA content (Q1 and Q2 cells) are present, and the fate of these resting cells was investigated after treatment with l‐β‐d‐arabinofuranosylcytosine (Ara‐C).
The experimental work consisted of growth curves, percentage of labelled mitoses curves after continuous labelling with 3H‐TdR, and cytophotometric determination of single‐cell DNA content in unlabelled tumour cells.
Treatment with an i.p. single injection of Ara‐C 200 mg/kg in the plateau JB‐1 tumour resulted in a significant reduction in the number of tumour cells 1 and 2 days later as compared with untreated controls, while no difference in the number of tumour cells was observed after 3 days. In tumours prelabelled with 3H‐TdR 24 hr before Ara‐C treatment, a significant decrease in the percentage of labelled mitoses was observed 6–8 hr later followed by a return to the initial value after 12 hr, and a new pronounced fall from 20 hr after Ara‐C. The second fall in the percentage of labelled mitoses disappeared when the labelling with 3H‐TdR was continued also after Ara‐C treatment. Cytophotometry of unlabelled tumour cells prelabelled for 24 hr with 3H‐TdR before Ara‐C treatment showed 20 hr after Ara‐C a pronounced decrease in the fraction of Qt cells paralleled by an increase in the fraction of unlabelled cells with S DNA content.
These results indicate recycling of resting cells first with G2 and later with Gx DNA content, which contribute to the regrowth of the tumours.