title: Development of latent residual drug damage to the hematopoietic marrow during the subsequent growth of tumors.
abstract: Growth of the Lewis lung (LLca) tumor in BDF1 mice was found to be accompanied by a marked expansion of the multipotential stem (CFUs-8) and committed erythroid (BFUe) and myeloid (CFU-gm) progenitor cells of the marrow with a concomitant depression of more differentiated compartments. The long-term effects of adriamycin (AdR), busulfan (BU), cis-diaminedichloroplatinum II (DDP), and 5-fluorouracil (5-FU) on the LLca-induced expansion of the CFUs-8 and CFU-gm were investigated at eight weeks after drug treatment. Of the four drugs studied, only BU demonstrated a reduction of CFUs-8 at eight weeks after treatment and prior to tumor inoculation. However, all of the drugs were found to prevent the expansion of the CFUs-8 compartment after 16 days of tumor growth. BU also resulted in a depressed CFU-gm compartment at the time of tumor inoculation, while CFU-gm in ADR-, DDP-, and 5-FU-treated animals was either at control levels (AdR), or unexpectedly elevated (DDP and 5-FU). Similar to the observations made for CFUs-8, all drugs prevented the expansion of the CFU-gm associated with tumor growth. The data suggest that qualitative differences observed between the long-term effects of the drugs on the marrow compartments may be more accurately related to the temporal "fixation" of residual drug damage brought about by enhanced differentiation of a drug-limited pluripotential CFUs, than to the actual magnitude of hematopoietic damage.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002066:Busulfan / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity; D003114:Colony-Forming Units Assay; D004317:Doxorubicin / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D005472:Fluorouracil / Q000633:toxicity; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D002066:Busulfan; D002945:Cisplatin; D005472:Fluorouracil