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.
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.
Baumgart
J
J
Central Institute of Microbiology and Experimental Therapy, Academy of Sciences of the German Democratic Republic, Jena.
Zhukovskaya
N V
NV
Anisimov
V N
VN
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D007941:Leukemia P388 / Q000188:drug therapy / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D051381:Rats; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000473:pathology*
D000970:Antineoplastic Agents; C037931:1,4-benzoquinone guanylhydrazone thiosemicarbazone; D008935:Mitoguazone; D005472:Fluorouracil