Genetic Determination of Regressive Pattern of Walker 256 Carcinosarcoma in Rats with Hypothalamic Diabetes Insipidus.

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.

Dynamics of tumor growth in Brattleboro and WAG rats injected with Walker 256 carcinosarcoma cells in different doses.

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.

Structure and concentration capacity of the kidneys in brattleboro rats under conditions of long-term vasopressin treatment.

The function and histochemistry of the kidney were studied in homozygous Brattleboro rats after 28-day treatment with exogenous arginine-vasopressin. The long-lasting effect of the hormone includes normalization of osmotic concentration, decrease in the number of b-glucuronidase granules in the medulla, and increasing content of hyaluronan in the interstitium. These changes promote physiological optimization of the antidiuretic reaction to vasopressin.

Decrease in the response to ADH of the rat kidney as a result of early postnatal treatment with cortisol.

Wistar rats were injected just once, intraperitoneally with cortisol (1 microgram/g) or saline at the age of 5 days. The cortisol-treated rats did not differ significantly in the (U/P)osm ratio from the saline-treated controls before 15 days of life. Their response to ADH was distinct but weaker than in the saline controls aged 30 days. This reduced response persisted to 60 days of life. In the collecting tubule fragments, (3H)AVP specific binding was lower in the cortisol-treated rats than in the controls at the age of 20 and 60 days. There was no (3H)AVP specific binding in the proximal convoluted tubules in the cortisol- and saline-injected rats of both ages. The ontogenetic patterns of cAMP specific binding in the papillary cytosolic fraction were different: the early increase in cAMP binding was protracted in the cortisol-treated rats, and no peak appeared at the age of 25 days. Cytosolic protein kinase activity was lower, no peak appeared at 30 days, no activation of protein kinase occurred to the end of weaning in the cortisol-treated rats. The difference between the cortisol and saline groups was abolished by day 30. The interference of cortisol with the ontogenetic changes in AVP binding capacity and cAMP-dependent protein kinase appears to be a plausible cause of the altered development of the response to ADH.