Diversity of penetration of anti-cancer agents into solid tumours.
Failure of anti-cancer agents to reach all clonogenic cells at cytotoxic concentrations is recognized as an important form of resistance in solid tumours. Subcutaneously implanted mammary adenocarcinoma 16/C was used to evaluate the intratumour distribution of five alkylating, bioreductive alkylating and intercalating agents and two radiation sensitizers. The agents were classified according to their in vivo distribution in well- and poorly-perfused tumour regions, as delineated by lissamine green. The classifications were: (1) distribution in direct proportion to the vascular supply; (2) uniform distribution to well- and poorly-perfused tumour regions; and (3) preferential retention in the poorly-perfused tumour regions. Our current state of knowledge did not allow reliable prediction of the classification based on chemical structure or mechanism of action.
Simpson-Herren
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Southern Research Institute, Birmingham, AL 35255-5305.
Noker
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PE
D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D000477:Alkylating Agents / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D000983:Antipyrine / Q000378:metabolism; D001692:Biological Transport; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007700:Kinetics; D008558:Melphalan / Q000378:metabolism / Q000627:therapeutic use; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D008558:Melphalan; D000983:Antipyrine