The effects of perfluorochemicals on tumor growth and chemotherapy response.
Hypoxia, leading to cells in resting or slow replication phases may be a cause of chemotherapy and radiation therapy resistance in some tumors. Perfluorochemicals (PFC) may potentiate response to these therapies by increasing oxygen delivery to the tumor, forcing cells into more therapy-responsive replicating phases. To assess the effects of PFC on tumor growth and chemotherapy response, 91 ACI rats bearing 1 cc flank Morris hepatoma tumors were divided into groups: Group I, control; Group II, Adriamycin (ADR) 10 mg/kg intraperitoneally (IP); Group III, Cytoxan (CTX) 100 mg/kg IP; Group IV, PFC 20 mL/kg IV; Group V, ADR and PFC; Group VI, CTX and PFC. Animals were kept in 0.5 FiO2 for 24 hours after treatment, and mortality and tumor volumes determined 2 weeks later. Tumor DNA turnover was measured using opposing pathways assay of 14C-thymidine uptake and degradation. In a separate group, tumor tissue pO2 was measured polarographically with an oxygen microelectrode before and after injection of PFC (20 mL/kg). The survival was significantly reduced in group IV (4%) compared with group I, control (73%). Both ADR and CTX slowed the growth of the tumor, while PFC alone significantly accelerated tumor growth. The tumor response to ADR was potentiated by the addition of PFC. These results were confirmed by DNA synthesis evaluation. The mean pO2 level prior to injection was 6.6 +/- 1.96 mmHg compared with 18.92 +/- 1.00 mmHg after PFC injection (P less than or equal to .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, Cardinal Glennon Children's Hospital, St Louis, MO 63104.
T R
TR
Weber
S H
SH
Westfall
L E
LE
Webb
R H
RH
Connors
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000378:metabolism / Q000627:therapeutic use; D004317:Doxorubicin / Q000378:metabolism / Q000627:therapeutic use; D004347:Drug Interactions; D007275:Injections, Intravenous; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D013936:Thymidine
D000970:Antineoplastic Agents; D004317:Doxorubicin; D003520:Cyclophosphamide; D013936:Thymidine