Development of resistance to 9-hydroxyellipticine in Chinese hamster lung cells is associated with a loss of oncogenic potential. In order to determine whether these phenotypical traits are the consequences of the same biochemical modification, or whether they can be dissociated, we have studied their expression in intraspecies hybrids between sensitive and resistant cells. Thirteen hybrid clones were thus examined. At early passages after fusion, they displayed drug sensitivities intermediate to those of parental cells, but relatively close to that of the sensitive parent. Upon injection into nude mice, these clones exhibited variable oncogenic potentials. These variations were independent of the drug sensitivity.

After further growth in the presence of 9-hydroxyellipticine, the hybrid cells recovered the drug resistance of the resistant parent. Yet, most of them remained clearly tumorigenic. Finally, the tumors produced by injection of the initial hybrids to nude mice were explanted in culture and then tested again for their drug sensitivity and tumorigenicity. These cells displayed both the tumorigenicity of the sensitive parent and the resistance of the resistant parent. Karyological analyses at the different steps of this work did not reveal any significant change which could be related to modifications of the expression of the characters studied.

Our results show that the loss of tumorigenicity and the resistance to 9-hydroxyellipticine can be expressed independently and cannot be accounted for by a unique biochemical alteration.

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Supported by the Centre National de la Recherche Scientifique (L.A.147), the Institut National de la Santé et de la Recherche Médicale (U.140), and the Commissariat à l'Energie Atomique.

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