Heavy water enhances the antineoplastic effect of 5-fluoro-uracil and bleomycin in nude mice bearing human carcinoma.
The antineoplastic effect of heavy water on the growth of xenotransplanted human carcinoma was compared to that of 2 cytostatic drugs. Seven-week-old BALB/c-nu/nu mice were inoculated subcutaneously with a poorly differentiated oropharyngeal squamous-cell carcinoma, or with variants of carcinoma of the large intestine. After tumor inoculation, 3 subgroups of mice were treated by: (i) moderately deuterated drinking water; (ii) i.p. injections of 5-Fluoro-uracil (5-FU) or Bleomycin; (iii) a combination of deuterated drinking water and of the cytostatic drugs. Control mice were not treated. Heavy water delayed growth of all carcinoma variants. The cytostatic drugs slowed down the growth of the 2 poorly differentiated tumor variants. Conversely, 5-FU did not retard the growth of the moderately well differentiated colon carcinoma. Heavy water combined with either cytostatic drug showed synergistic effects in the 2 poorly differentiated tumor variants. The tumors of treated animals weighed 36% to 90% less than those of control animals. The antineoplastic effects were more conspicuous in poorly than in moderately well differentiated tumor variants. Cytokinetic parameters such as labelling indices following application of 5-125I-Iodo-2'deoxyuridine, and of Ki-67, a monoclonal antibody (MAb) directed against an antigen of proliferating cells, or mitotic indices and tumor volume doubling time, combined with the results of histologic evaluation of the tumors, suggested an underlying deuterium-induced prolongation of tumor-cell cycle times and a reduction of the growth fraction.
Institute of Pathology, University of Bern, Switzerland.
H J
HJ
Altermatt
J O
JO
Gebbers
J A
JA
Laissue
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001761:Bleomycin / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003903:Deuterium / Q000627:therapeutic use*; D004357:Drug Synergism; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009368:Neoplasm Transplantation; D013047:Specific Pathogen-Free Organisms
D001761:Bleomycin; D003903:Deuterium; D005472:Fluorouracil