Details of Walker 256 carcinosarcoma growth in Brattleboro and ISIAH lines of rats

The growth dynamics of transplantable Walker 256 carcinosarcoma was investigated in rats modeling inherited systemic pathological processes. Hypothalamic diabetes insipidus is developing in Brattleboro rats on the background of total vasopressin absence in the blood. Regulation of water-electrolytic metabolism is disturbed due to hormonal disbalance. ISIAH rats are carriers of inherited stress-induced arterial hypertension. Vascular rigidity is accompanied by additional pleiotropic effects. The experiments have been carried out on inbred Brattleboro and ISIAH rats, and their hybrids segregated from (ISIAH × Brattleboro) F1 × Brattleboro mating. The mutant vasopressin gene di (diabetes insipidus) and fur painting genes, albino (C) and hooded (h), localized in three different linkage groups, were used as genetic markers of progeny splitting. Alternative pairs of traits were: daily water consumption above 45 % or lower than 20 % of body weight – for the vasopressin locus; total white or other color of fur – for the albino locus; presence or absence of unevenness in fur painting – for the hooded locus. It has been found that there are only two types of growth dynamics of grafted tumor. In the rats of the inbred Brattleboro line and in the didi homozygotes, which were segregated from analytical mating (ISIAH × Brattleboro) F1 × Brattleboro, tumor began to regress and diminished until absolute disappearance after some initial growing. Heterozygous offspring di+ and parental ISIAH rats with the normal vasopressin genotype (++) showed permanent tumor growth until lethal injury. It was found that tumor regression demonstrates concordance exclusively to the didi genotype, segregation of this feature does not depend on the genotype of the albino or hooded loci. Alternative to tumor regression, permanent growth of tumor is observed in all rats having at least one normally expressed vasopressin gene.

1. Bender K., Adams M., Baverstock P.R., den Biemann M., Bissbort S., Brdicka R., Butcher G.W., Cramer D.V., von Deimling O., Festing M.F.W., Gunter E., Guttmann R.D., Hedrich H.J., Kendall P.B., Kluge R., Moutier R., Simon B., Womack J.E., Yamada J., van Zutphen B. Biochemical markers in inbred strains of the rat (Rattus norvegicus). Immunogenetics. 1984;19:257-266.

2. Khegai I.I. Specific expression of gene di (diabetes insipidus) in homologous inbred rat lines. Rus. J. Genet. 2002;38(12):1424-1427.

3. Khegai I.I. Phenotypic expression of the mutant gene diabetes insipidus in rats and criteria of genotyping by phenotype. Rus. J. Genet. 2003;39(1):57-60.

4. Khegay I.I, Golubjatnikova A.V. Localization in the fourth linkage group of a gene di affecting diabetes insipidus in rats. Biochem. Genet. 1993;31(3/4):201-204.

5. Khegai I.I., Melnikova V.I., Popova N.A., Zakharova L.A., Ivanova L.N. The effect of vasopressin on the Zajdela hepatocellular carcinoma growth rate. Doklady Biol. Sci. 2014;457(3):222-224.

6. Khegai I.I., Melnikova V.I., Popova N.A., Zakharova L.A., Ivanova L.N. The effect of vasopressin on Seidel’s hepatocellular carcinoma growth rate. Doklady Akademii Nauk = Proceedings of the Russian Academy of Sciences. 2014;457(3):363-365.

7. Khegai I.I., Popova N.A., Zakharova L.A., Ivanova L.N. Walker 256 tumor growth in rats with hereditary defect of vasopressin synthesis. Bul. Exp. Biol. Med. 2006;142(3):344-346.

8. Khegai I.I., Popova N.A., Zakharova L.A., Ivanova L.N. Walker 256 tumor growth in rats with a hereditary defect of vasopressin synthesis. Byulleten eksperimentalnoy biologii i meditsiny = Bulletin of experimental biology and medicine. 2006;142(9):316-318.

9. Markel A.L. Development of a new strain of rats with inherited stressinduced arterial hypertension. In: Genetic hypertension. Volume 218. Sassard J., editor. London: Colloque INSERM; 1992:405-407.

10. O’Brien S.J. Genetic Maps. Cold Spring Harbor Laboratory. 1987;4: 464-469.

11. Redina O.E, Klimov L.O., Ershov N.I. , Abramova T.O., Ivanova L.N., Markel A.L. The downregulation of genes controlling vascular tone in kidneys of ISIAH rats with stress-induced arterial hypertension. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2014;18(4/2):910-919.

12. Redina O.E, Klimov L.O., Ershov N.I., Abramova T.O., Ivanova L.N., Markel A.L. The decreased expression of genes controlling the vascular tone in the kidneys of ISIAH rats with stress-induced arterial hypertension. Rus. J. Genet.: Appl. Res. 2015;5(4):340-347. DOI 10.1134/S2079059715040127

13. Schmale H., Richter D. Single base deletion in the vasopressin gene is the cause of diabetes insipidus in Brattleboro rats. Nature. 1984; 308:705-709.

14. Valtin H. The discovery of the Brattleboro rat, recommended nomenclature, and the question of proper controls. Ann. N.Y. Acad. Sci. 1982;394:1-9.

15. Vrionis F.D., Wu J.K., Qi P., Cano W.G., Cherington V.J. Tumor cells expressing the herpes simplex virus-thymidine kinase gene in the treatment of Walker 256 meningeal neoplasia in rats. J. Neurosurg. 1996;84:250-257.