Lymphocytes anticancer chemosensitivity testing in vitro--an approach to predict immunosuppressive effect of anticancer agents.
In an attempt to predict immunosuppression by chemotherapy, an in vitro lymphocytes chemosensitivity assay was developed. The effect of mitomycin C (MMC), carboquone (CQ), adriamycin (ADR) and 5-fluorouracil (5-FU) on spleen cells of BALB/c mice were assessed by phytohemagglutinin (PHA) response inhibition assay. ADR and 5-FU highly suppressed PHA response, whereas MMC or CQ had only a slight influence. The administration of ADR or 5-FU to mice resulted in a significant decrease of peripheral blood lymphocytes and cortical thymocytes in number, and pretreatment with ADR or 5-FU prior to tumor inoculation shortened the survival time of the mice. All these four agents highly suppressed in vitro DNA synthesis of MOPC-104E plasmacytoma, but ADR or 5-FU did not induce complete regression of the tumor. MMC or CQ induced complete regression of MOPC-104E, but they did not induce complete regression of the tumor transplanted in athymic nude mice. These results suggest that T cells participate in tumor regression and immunosuppression reduces antitumor activity of the host and that PHA response inhibition assay may be useful to predict immunosuppressive effect of anticancer agents.
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First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Imai
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Shiraishi
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Ohgaki
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K
Tobe
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002225:Carbazilquinone / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D007166:Immunosuppressive Agents; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D010954:Plasmacytoma / Q000188:drug therapy; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D008937:Mitomycins; D002225:Carbazilquinone; D016685:Mitomycin; D004317:Doxorubicin; D005472:Fluorouracil