Development of MeCCNU-resistance in clonally derived lines of Lewis lung carcinoma.

The development of resistance to MeCCNU in four clonal lines of Lewis lung carcinoma derived from lung colonies has been examined. Treatment of the clones with 15 mg/kg MeCCNU once in each in vivo passage resulted in a rapid reduction in tumour responsiveness to this drug. This shows that MeCCNU resistance can arise at rates which may be applicable in spontaneous tumours and their metastases. Karyotypic heterogeneity was evident very early after isolation of the clones and this has potentially important implications for the experimental use of clones and for the features of metastatic disease. Karyotype analysis of one of the clones at each passage suggested that development of resistance was associated with the selection of a single sub-population of tumour cells but the kinetics of resistance development cannot be totally explained in terms of this simple selection.