The unique sensitivity of Walker rat tumour cells to difunctional agents is associated with a failure to recover from inhibition of DNA synthesis and increased chromosome damage.

The rate and mode of DNA synthesis was examined by thymidine uptake and by flow cytometry in Walker tumour cells highly sensitive to difunctional agents (WS), and in a derived subline of resistant cells (WR) (Rawlings and Roberts, 1986), following their treatment with sulphur mustard. Both cell lines exhibited the same dose-dependent and progressive depression in rate of DNA synthesis for up to 4 h after treatment. Thereafter the depression in rate of synthesis was partially reversed in the WR cells but DNA synthesis continued to decrease in the WS cells resulting in their slower transit through the S phase and a persistent block in the G2/M phase of the cell cycle. Sensitive cells which finally escaped the block in G2 carried more chromosome aberrations than the corresponding resistant cells. Neither cell line was defective in daughter strand-gap repair. In their sensitivity to difunctional but not to monofunctional compounds, their failure to recover from the early depression of DNA synthesis, their apparent lack of a defect in excision repair and their sensitivity to chromosome aberration induction, the Walker cell phenotype closely resembles that of the human Fanconi's anaemia cell.