Negative impact of cancer chemotherapy on protein metabolism in healthy and tumor-bearing rats.
Although chemotherapeutic agents are widely used in the treatment of cancer, few experimental data are available on their effects on host N metabolism. We studied the effects of a single intraperitoneal (IP) injection of cyclophosphamide ([CYP] 120 mg/kg), 5-fluorouracil ([5-FU], 50 mg/kg), cisplatinum ([CDDP], 5 mg/kg), or methotrexate ([MTX], 30 mg/kg). N balance was studied for 6 days following chemotherapy in healthy rats (n = 40) and in rats bearing Morris Hepatoma 7777 ([MH7777] n = 40) in a situation comparable to that of human cancer (tumor burden < 0.2% of body weight, moderate anorexia, and weight loss). In healthy rats, all drugs induced transient body weight loss, anorexia, and poor N balance. At day 6 posttreatment, all animals had resumed normal feed intake and positive N balance except CDDP-treated rats, which showed continued weight loss and poor N balance. CDDP and MTX exhibited antitumor activity; however, CDDP induced diarrhea in six of eight tumor-bearing rats. Drug-induced anorexia was more severe in tumor-bearing than in healthy treated rats. N balance was more severely decreased in MH7777-bearing rats than in healthy treated animals in response to 5-FU (159 +/- 36 v 273 +/- 27 mg N/2 d) and MTX (-66 +/- 36 v 153 +/- 37 mg N/2 d) at days 3 to 4 postinjection. These results establish the presence of drug-specific effects on host N balance and the existence of a drug-tumor interaction for N metabolism in the tumor-bearing host.
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002100:Cachexia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004247:DNA / Q000032:analysis / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D007421:Intestine, Small / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009584:Nitrogen / Q000032:analysis / Q000378:metabolism / Q000652:urine; D009929:Organ Size; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss / Q000502:physiology
D000970:Antineoplastic Agents; D011506:Proteins; D012313:RNA; D003520:Cyclophosphamide; D004247:DNA; D009584:Nitrogen; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate