Immunotoxic and cancerostatic effects of ethyl-4-isothiocyanatobutanoate in female Lewis rats with implanted fibrosarcoma.
Isothiocyanates (ITCs) have been isolated from plants. Naturally occurring and synthetic ITCs are known as effective chemopreventive agents. Ethyl 4-isothiocyanatobutanoate (E-41B) is a derivative of gamma-aminobutyric acid. Immunotoxic and canocerostatic effects of E-41B in female inbred Lewis rats implanted with experimental fibrosarcoma BP6-TU2 was evaluated in this study. On day 5 after subcutaneous application of tumor cells, animals started to be treated intraperitoneally three times a week with two different doses of E-41B: 28 and 35 mg/kg/day during 28 days. High dose of E-41B was close to maximum tolerated dose (MTD). Control groups of rats with or without tumors injected intraperitoneally only saline or 70% dimethylsulphoxide were added. Administrating of E-41B resulted in suppression of thymus, popliteal lymph node, spleen weight and spleen cellularity. Hematologic evaluation displayed decreased erythrocyte (ERY) count and level of hemoglobin (HB) in rats treated withE-41B. Immune assays--the phagocytic activity of polymorphonuclear leukocytes (PMN) and monocytes, primary antibody response and in vitro proliferative activity of spleen lymphocytes (LY) to mitogens were not significantly affected by E-41B treatment E-41B moderately decreased tumor weights, but this decrease was not statistically significant in comparison with DMSO-exposed rats with tumors. The fibrosarcoma implantation itself increased significantly spleen weight and changed hematological parameters (decreased HB, increased mean cell volume of ERY, increased leukocyte count, increased % PMN, decreased % LY, decreased % EO). Moreover, moderate decreased percentage of CD161+ positive cells (NK cells) were found in peripheral blood. Immune assays showed decline in proliferation of lymphocytes and phagocytic activity of leukocytes. Our findings indicate that administration of E-41B displayed hematoxic effect in rats implanted with fibrosarcoma. Immunotoxic effect was shown as decreased lymphoid organ weight and spleen cytotoxicity although function of immune cells was not impaired.
Sovcikova
Andrea
A
Department of Biochemistry and Microbiology, Slovak University of Technology, Bratislava, Slovakia.
Tulinska
Jana
J
Chalupa
Ivan
I
Liskova
Aurelia
A
Kuricova
Miroslava
M
Horvathova
Mira
M
Seemannovaa
Zuzana
Z
Horakova
Katarina
K
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D002087:Butyrates / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000276:immunology; D017879:Isothiocyanates / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology; D009929:Organ Size / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D002087:Butyrates; D017879:Isothiocyanates; C082832:ethyl 4-isothiocyanatobutanoate