title: Survival of rat mammary tumor cell clones and DNA strand damage following adriamycin treatment.
abstract: Tumor cell subpopulations have been shown to be heterogeneous in a number of phenotypic characteristics, including responses to cytotoxic drugs. This phenotypic heterogeneity has been used here to study mechanisms associated with Adriamycin (doxorubicin HCl)-induced cytotoxicity. Clonogenic survival and alkaline elution methods were employed to examine the response of two tumor cell subpopulations to Adriamycin. The cells were derived from a primary 13762NF rat mammary adenocarcinoma (clone MTC) and a lung metastasis in the same animal (clone MTLn3). The MTC cells were significantly more resistant to Adriamycin than were the MTLn3 cells; the dose effective in reducing cell survival by 50% was 10-fold higher. Protein-associated DNA strand breakage assayed by alkaline elution was dose-dependent in both clones, and MTC cells were again more resistant to break induction than were MTLn3. These results showed that clonal tumor subpopulations isolated from a primary tumor and its metastases possessed different intrinsic survival responses to Adriamycin treatment in vitro and that this survival response correlated with Adriamycin-induced production of protein-associated DNA single-strand breaks.
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051381:Rats
chemical_list: D004317:Doxorubicin; D004247:DNA