title: Immunotoxic and cancerostatic effects of ethyl-4-isothiocyanatobutanoate in female Lewis rats with implanted fibrosarcoma.
abstract: 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.
authors.affiliation: Department of Biochemistry and Microbiology, Slovak University of Technology, Bratislava, Slovakia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sovcikova
authors.forename: Jana
authors.initials: J
authors.lastname: Tulinska
authors.forename: Ivan
authors.initials: I
authors.lastname: Chalupa
authors.forename: Aurelia
authors.initials: A
authors.lastname: Liskova
authors.forename: Miroslava
authors.initials: M
authors.lastname: Kuricova
authors.forename: Mira
authors.initials: M
authors.lastname: Horvathova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Seemannovaa
authors.forename: Katarina
authors.initials: K
authors.lastname: Horakova
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D002087:Butyrates; D017879:Isothiocyanates; C082832:ethyl 4-isothiocyanatobutanoate