title: Sodium valproate enhances urethane tumorigenicity in lungs of male but not female mice.
abstract: In the study, the possible effect of sodium valproate (NaVP) on urethane-induced lung tumors in mice has been evaluated. BALB/c mice (n = 120; 4-6 weeks old, both sexes) were used in the following groups: 1) urethane-treated, 2) urethane-NaVP-treated, 3) only NaVP-treated, 4) control. In the same groups, castrated male mice (n = 48) were investigated. Urethane was given by intraperitoneal injections 10 mg/mouse, twice a week, the total dose 50 mg/mouse. In NaVP-treated mice, the 0.4 % NaVP aqueous solution was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in urethane-NaVP-treated males was significantly higher than in those treated with urethane only (13.82 ± 1.12 vs 6.77 ± 0.43, p < 0.0001). No significant difference in the number of tumors per mouse was revealed while comparing the female urethane- and urethane-NaVP-treated groups (6.50 ± 0.79 vs 8.15 ± 0.55, p = 0.105). No difference in the number of tumors per mouse was found in urethane-NaVP-treated castrated males as compared with urethane-treated castrated males. However, in the urethane-NaVP-treated castrated males the number of tumors per mouse was significantly lower than in analogous non-castrated males (7.8 ± 1.67 vs 13.82 ± 1.12, p < 0.01). NaVP combined with urethane potentiates urethane tumorigenicity in BALB/c non-castrated but not in female and castrated male mice. These data indicate an important role of testosterone in the urethane-NaVP induced lung tumorigenesis.
authors.affiliation: Laboratory of Carcinogenesis and Tumor Pathophysiology, Institute of Oncology, Vilnius University, Vilnius, Lithuania ; Mykolas Romeris University, Vilnius, Lithuania.
authors.forename: Donatas
authors.initials: D
authors.lastname: Stakisaitis
authors.affiliation: Laboratory of Carcinogenesis and Tumor Pathophysiology, Institute of Oncology, Vilnius University, Vilnius, Lithuania.
authors.forename: Saule
authors.initials: S
authors.lastname: Uleckiene
authors.affiliation: Laboratory of Carcinogenesis and Tumor Pathophysiology, Institute of Oncology, Vilnius University, Vilnius, Lithuania.
authors.forename: Janina
authors.initials: J
authors.lastname: Didziapetriene
authors.affiliation: Lithuanian University of Health Sciences, Department of Histology and Embryology, Kaunas, Lithuania.
authors.forename: Angelija
authors.initials: A
authors.lastname: Valanciute
authors.affiliation: Lithuanian University of Health Sciences, Department of Histology and Embryology, Kaunas, Lithuania.
authors.forename: Raminta
authors.initials: R
authors.lastname: Mozuraite
authors.affiliation: Lithuanian University of Health Sciences, Veterinary Academy, Kaunas, Lithuania.
authors.forename: Paulius
authors.initials: P
authors.lastname: Matusevicius
keywords: gender differences; lung tumorigenesis; mice; sodium valproate; urethane