Potential of continuous tumour cell lines for establishing patterns of cross-resistance and collateral sensitivity in...

The potential value of continuous tumour cell lines for establishing in vitro patterns of cross-resistance and collateral sensitivity has been examined. Results are presented for a series of sublines of the murine L5178Y lymphoma in which resistance has been induced in vitro by repeated exposure to the following antitumour drugs: methotrexate, 5-fluorouracil, adriamycin, vincristine and vindesine. A comparison has also been made between data derived from a murine (L5178Y) and a human tumour (LoVo) cell line, derived from a colon carcinoma, in which 5-fluorouracil resistance has been induced. Preliminary results suggest that the human tumour model may be more relevant clinically. It has also been demonstrated that prior exposure to fractionated X-irradiation in vitro can result in the expression of resistance or collateral sensitivity, depending on the drug evaluated. Furthermore, the expression of cross-resistance to certain drugs appears to differ, depending on the method used to induce or select for resistance in vitro. If confirmed, these latter observations may have major clinical implications for the combined modality approach to cancer treatment.