title: Effect of high cell density on the growth properties of tumor cells: a role in tumor cytotoxicity of chemotherapeutic drugs.
abstract: The aim of this study was to understand the role of tumor progression in the growth properties of tumor cells and their susceptibility to the cytotoxicity of chemotherapeutic drugs. A murine transplantable T cell lymphoma of spontaneous origin, designated as Dalton's lymphoma, was used as a model tumor for this investigation. Tumor cells were harvested from the early (5 days after tumor transplantation) and late tumor-bearing stages (17 days after tumor transplantation), with or without in-vivo administration of the chemotherapeutic drugs, cisplatin or doxorubicin. Tumor cells harvested at the late tumor-bearing stages showed a higher proliferative ability in vitro. Tumor progression was found to be associated with a decline in the tumor cytotoxicity of the chemotherapeutic drugs. Similar results were also obtained when tumor cells were cultured at low (10(5) cells/ml) and high (10(9) cells/ml) cell densities in vitro in medium alone or in one containing the chemotherapeutic drugs. An increase in the expression of heat shock protein (Hsp70), vascular endothelial growth factor, interleukin-2 receptor and interleukin-2 proteins along with an inhibition in the expression of caspase-activated DNase and p53 proteins was observed during the late tumor-bearing stage and also in the Dalton's lymphoma cells when cultured in vitro at a higher cell density. The ascitic fluid obtained from the late tumor-bearing stage and the culture supernatant of tumor cells incubated in vitro at high cell density showed high levels of cell growth-regulating cytokines: interleukin-1, interleukin-2, interferon-gamma, vascular endothelial growth factor, tumor growth factor-beta and interleukin-10. In-vivo administration of cisplatin in tumor-bearing mice at the late tumor-bearing stage did not alter the level of these cytokines in the ascitic fluid. In view of the results of this investigation, it is suggested that under high cellular density-associated environmental conditions the tumor cells alter their growth properties depending on an alteration in the expression of cell growth and apoptosis-regulating proteins. Tumor cells, thus, switch to a high level of proliferation, which renders them resistant to the cytotoxicity of chemotherapeutic drugs.
authors: School of Biotechnology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors: Vivek
authors: V
authors: Singh
authors: Sukh Mahendra
authors: SM
authors: Singh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001202:Ascitic Fluid / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D003470:Culture Media; D004317:Doxorubicin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation
chemical_list: D000970:Antineoplastic Agents; D003470:Culture Media; D004317:Doxorubicin; D002945:Cisplatin