Comparison of early onco/suppressor gene expressions in peripheral leukocytes and potential target organs of rats exposed to the carcinogen 1-nitropyrene.

An in-vivo model has been developed to study early expressions of c-myc, Ha-ras oncogenes and p53 suppressor gene as biomarkers of carcinogenic exposure and/or tumorigenesis. In order to validate the in-vivo expression changes as biomarkers, rats were treated with the outdoor air pollutant carcinogen 1-nitropyrene. The gene expression levels were measured after 24 and 48 h in potential target tissues (lung, liver, lymph nodes, kidneys, spleen) and in peripheral blood leukocytes. Another main objective was to prove the applicability of leukocytes as a surrogate tissue, having a similar expression pattern of the selected genes upon carcinogenic exposure. The c-myc oncogene was not suitable as an early biomarker because of the lack or low level of its expression. However, in the case of the other oncogene Ha-ras and the suppressor gene p53, remarkable and early changes were detected in the expression signals. Similar expression patterns could only be detected in leukocytes and the spleen; therefore we continue this validation study by using other types and routes of exposure.

Deleterious action of vasopressin in gastroduodenal ulceration: experimental and clinical observations.

Vasopressin, released from the posterior pituitary and from the vascular endothelium, can cause vasoconstriction and provoke platelet aggregation, leading to an impaired tissue blood supply. In humans with pituitary diabetes insipidus the central release of vasopressin is diminished, and in the Brattleboro homozygous rat there is congenitally no synthesis of this hormone. The gastroduodenal intramucosal vasopressin level is elevated in normal rats following various acute ulcerogenic challenges (after ethanol, reserpine, indomethacin, cold-restraint stress, endotoxin shock and hemorrhagic shock), and vasopressin-deficient rats are less sensitive to these stimuli. In a hospital- and population-based case-control, age-matched retrospective study, the incidence of human gastroduodenal ulceration is significantly higher in the normal population (in whom the release of vasopressin is presumed to be intact) than in the vasopressin-deficient one (central diabetes insipidus patients). In conclusion, endogenous vasopressin plays an aggressive role in development of gastroduodenal ulceration, especially that related to stress.