pituitrin and Carcinoma-256--Walker

We studied the growth dynamics of Walker 256 carcinosarcoma in recombinant progeny of dihybrid crosses of Brattleboro and WAG rats. A mutation in the vasopressin gene determining hypothalamic diabetes insipidus was detected in Brattleboro rats. WAG rats are carriers of normal vasopressin gene. Another interlinear difference was linked to tyrosinase gene controlling melanin synthesis. WAG rats express mutant allele determining albino phenotype. Brattleboro rats had normal working tyrosinase gene. F2 segregation yielded phenotypic classes with two patterns of tumor growth: linear growth or regression. Tumors regression was not linked to tyrosinase activity and was observed only in rats with diabetes insipidus. Analysis of mutants in next generations F3 and F4 confirmed this regularity in the Walker 256 carcinosarcoma growth pattern.

Topics: Animals; Carcinoma 256, Walker; Carcinosarcoma; Diabetes Insipidus; Diabetes Mellitus; Melanins; Monophenol Monooxygenase; Rats; Rats, Brattleboro; Vasopressins

Walker 256 carcinosarcoma is a transplantable model of rat carcinoma that originally appeared spontaneously in mammary glands. The growth rate of Walker 256 carcinosarcoma in vasopressin-deficient Brattleboro rats is lower than in WAG rats and their congenic hybrids with normal vasopressin levels. Study of tumor proteins detected essential alterations. Tumor regression starting at the 14th day in Brattleboro rats was accompanied by changes in the laminin pattern. At the 21st day, the concentration of α-chains became twice as low, while β-chains of laminin showed a sixfold increase compared to the initial equimolar correlation of bands. Congenic hybrids having one active copy of the vasopressin gene to provide a physiological level of hormone against the genetic background of Brattleboro rats show the same laminin alterations as WAG rats. They demonstrated a similar moderate increase of γ-chains and threefold growth of α- and β-chains of laminin in tumor tissue. It is supposed that vasopressin may be involved in the regulation of relevant local stimuli to trigger renovation of the laminin composition in a course of growing Walker 256 carcinosarcoma.

Topics: Animals; Carcinoma 256, Walker; Chimera; Crosses, Genetic; Disease Progression; Gene Expression Regulation, Neoplastic; Laminin; Male; Neoplasm Regression, Spontaneous; Protein Isoforms; Rats; Rats, Brattleboro; Signal Transduction; Tumor Burden; Vasopressins

The growth features of Walker 256 carcinosarcoma in rats of different genotypes were investigated. The experiments has been carried out on rats of the inbred Brattleboro and WAG lines, as well as on their hybrids segregated during congenic translocation of the normal vasopressin gene to the genotype of the Brattleboro rats. Brattleboro rats do not express the vasopressin gene. It has been found that there are only two types of tumor growth dynamics. In rats of the inbred Brattleboro line and in homozygotes di/di, that were segregated by backcrossings of heterozygous offsprings from the original crossbreeding between (WAG x Brattleboro) F1 x Brattleboro and the individuals with parental Brattleboro genotype, having grown to some extent the tumor regresses and disappears. In hybrid heterozygous siblings of di/+ genotype tumor grows linearly with time and always leads to fatal outcome. It has been found that, in the congenic procedure, the tumor regression trait is stably maintained and persistently inherited in lineage concordantly with the di/di genotype and, in rats with at least one allele of a normally expressed vasopressin gene, continuous and lethal tumor growth is always observed.

Topics: Animals; Carcinoma 256, Walker; Gene Expression Regulation, Neoplastic; Heterozygote; Homozygote; Rats; Rats, Inbred Strains; Vasopressins

The growth pattern of carcinosarcoma Walker 256 was studied in rats with different levels of vasopressin in the blood. The Brattleboro rats are unable to synthesize vasopressin in a consequence of deletion in the coding gene. Hybrids from crossbreeding of the mutant Brattleboro and normal WAG rats inherit the one intact vasopressin gene and hold nearly normal hormone level. It was found that non-strain-specific carcinosarcoma Walker 256 intensively grows in WAG rats and their offsprings from crossbreeding with Brattleboro rats, and tumor development is equally terminated in them by death. Carcinosarcoma grows less intensely in Brattleboro rats; the tumor nodes increased only within the first 2 weeks, after which, the tumor began to decrease and eventually disappeared. Infusion of exogenous vasopressin to Brattleboro rats intensifies a tumor growth in the first 2 weeks after the inoculation of Walker 256 cells; however, it does not prevent a following regression and resorption of tumors.

Topics: Animals; Carcinoma 256, Walker; Cell Proliferation; Disease Models, Animal; Female; Male; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Neoplasm Transplantation; Rats; Rats, Brattleboro; Vasopressins

The peculiarities of Walker 256 tumor growth depending on the dose of transplanted cells were studied in rats differing by vasopressin production. Transplantation of 10(5) cells does not lead to tumor development. The dose of 7 x 10(5) cells induces progressively growing tumors in WAG rats, while in Brattleboro rats tumors regressed after a short period of growth. Increasing the dose to 2.8 x 10(6) cells was inessential for the dynamics of tumor growth in WAG rats, but stimulated regression of tumor growth in Brattleboro rats, producing no vasopressin. This dose dependence suggests the involvement of the immune system into the dynamics of tumor growth.

Topics: Animals; Carcinoma 256, Walker; Neoplasm Transplantation; Rats; Rats, Brattleboro; Rats, Wistar; Vasopressins

The growth pattern of the Walker 256 solid tumor has been studied in rats with different doses of the mutant vasopressin gene. In contrast to the vasopressin gene of normal WA rats, that of mutant Brattleboro rats has a deletion in the coding region that blocks expression at the translation level. The mutation is inherited as a recessive character and is expressed in homozygous Brattleboro rats as diabetes insipidus with an increased water consumption because of the absence of vasopressin in the blood. (WAG x Brattleboro) F1 hybrids have the same normal phenotype as WAG rats, including a low water consumption. Walker 256 carcinosarcoma, which is not strain-specific, intensely grows only in WAG and (WAG x Brattleboro) F1 rats. In these groups, the growth of the tumor leads to the animal death within approximately 30 days after the inoculation of tumor cells. In Brattleboro rats, the carcinosarcoma grows less intensely: the tumor node somewhat increases only within the first two weeks, after which the tumor began to decrease and eventually disappears altogether. Both characters exhibit a 100% concordance at the individual level.

Topics: Animals; Carcinoma 256, Walker; Drinking; Genes, Recessive; Homozygote; Mutation; Neoplasm Transplantation; Rats; Rats, Brattleboro; Rats, Mutant Strains; Species Specificity; Transplantation, Heterologous; Vasopressins

Stable deceleration of Walker 256 tumor growth was detected in Brattleboro rats with vasopressin synthesis defect in comparison with normal WAG rats. In contrast to continuous tumor growth typical of rats, the growth of this tumor in Brattleboro rats was negligible and was observed during the first 15-18 days after transplantation, after which the tumor regressed and disappeared. The effect was age-dependent and was more pronounced in old animals. Repeated injection of Walker 256 cells does not lead to tumor development, which attested to direct involvement of the immune system in the detected phenomenon.

Topics: Aging; Animals; Carcinoma 256, Walker; Neoplasm Transplantation; Rats; Rats, Brattleboro; Rats, Inbred Strains; Species Specificity; Vasopressins

There has been longstanding interest in the characteristics of "feeder vessels" to tumors. To develop a convenient model for assessing the determinants of the responsiveness of the arterial blood supply to tumors, we assessed by arteriography the response of the spermatic artery to norepinephrine, vasopressin, and ergonovine after implantation of Walker carcinoma in the testis of the rat. Loss of response to norepinephrine of the spermatic artery supply to the tumor occurred by the fourth day of tumor growth in this model, along the entire length of the spermatic artery. As expected, there was sustained vasoconstriction of the contralateral spermatic artery to the normal testis in response to norepinephrine. Vasopressin and ergonovine exerted no effect, so that the specificity of the loss of response to norepinephrine remains unclear. The spermatic artery provides an accessible and convenient model for studying the blood supply to tumors.

Topics: Animals; Arteries; Carcinoma 256, Walker; Ergonovine; Male; Neoplasm Transplantation; Norepinephrine; Rats; Rats, Inbred Strains; Testicular Neoplasms; Testis; Vasopressins