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Carcinogenesis and aging. VIII. Effect of host age on tumour growth, metastatic potential, and chemotherapeutic sensitivity to 1.4-benzoquinone-guanylhydrazonethiosemicarbazone (ambazone) and 5-fluorouracil in mice and rats.

Abstract
Mice and rats of various ages (3, 10-12, and 18-19 months) were inoculated with the transplantation tumours murine melanoma B16 (B16), mammary adenocarcinoma 755 (Ca-755), leukemia P388 (P388), and rat rhabdomyosarcoma RA-2 (RA-2). Subcutaneous (sc) growth of B16 was not markedly affected by the age of the syngeneic host whereas intravenously (iv) inoculated 12 months old C57BL/6 mice developed more pulmonary metastases than animals 3 months of age. Median survival time (MST) of 18 months old mice bearing Ca-755 was significantly shorter than that of younger individuals. In contrast, old rats that had been injected RA-2 iv survived longer than controls. Survival of DBA/2 mice inoculated intraperitoneally (ip) with P388 cells was not influenced by the age of the host. The antineoplastic activity of ambazone and, to a less extent, of 5-fluorouracil against P388 was drastically lower in 12 months old mice than in 3 months old tumour bearers. Likewise a graduate loss of antineoplastic activity of ambazone against Ca-755 was observed with increasing age of the mice, whereas the effect of ambazone and 5-fluorouracil against RA-2 did not depend on the age of the rats. It is suggested that tumour-host interactions as well as pharmacokinetics of a given drug may underlie age-related changes.
AuthorsJ Baumgart, N V Zhukovskaya, V N Anisimov
JournalExperimental pathology (Exp Pathol) Vol. 33 Issue 4 Pg. 239-48 ( 1988) ISSN: 0232-1513 [Print] Germany
PMID3229459 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • 1,4-benzoquinone guanylhydrazone thiosemicarbazone
  • Mitoguazone
  • Fluorouracil
Topics
  • Adenocarcinoma (drug therapy, pathology)
  • Aging (physiology)
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Cell Division
  • Female
  • Fluorouracil (therapeutic use)
  • Leukemia P388 (drug therapy, pathology)
  • Leukemia, Experimental (pathology)
  • Male
  • Mammary Neoplasms, Experimental (drug therapy, pathology)
  • Melanoma, Experimental (drug therapy, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Mitoguazone (analogs & derivatives, therapeutic use)
  • Neoplasm Metastasis
  • Rats
  • Rhabdomyosarcoma (drug therapy, pathology)

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