Developmental stage sensitivity and mode of action information for androgen agonists and antagonists.

Autor: McClain, D.E., Benson, K.A., Dalton, T.K., Ejnik, J., Emond, C.A., Hodge, S.J., Kalinich, J.F., Landauer, M.A., Miller, A.C., Pellmar, T.C., Stewart, M.D., Villa, V., Xu, J.
Předmět:
Zdroj: Science of the Total Environment. 7/2/2001, Vol. 274 Issue 1-3, p115. 4p.
Abstrakt: The response from exposure to a toxic agent during development may vary depending on the dose, time of exposure and the mode of action. The mode of action and developmental stage sensitivity are established only for a limited number of chemical classes. Some aspects of developmental stage sensitivity that appear to affect the response to androgen agonists and antagonists are the levels and distribution of endogenous androgens and the androgen receptor at particular times during development. This information is summarized and discussed as it relates to two critical windows of development: the period of male reproductive tract differentiation, and the peripubertal period when male sexual maturation occurs. Developmental stage sensitivity and mode of action data for the androgen antagonist vinclozolin are reviewed. Vinclozolin acts by binding to and activating the androgen receptor and affects a number of endpoints of reproductive tract differentiation as well as pubertal maturation. Approaches to incorporating mode of action, developmental stage sensitivity, and dose/potency information into risk assessment, as well as the additional data needed for using mode of action information, both quresearch. The Persian Gulf War resulted in injuries of US Coalition personnel by fragments of depleted uranium (DU). Fragments not immediately threatening the health of the individuals were allowed to remain in place, based on long-standing treatment protocols designed for other kinds of metal shrapnel injuries. However, questions were soon raised as to whether this approach is appropriate for a metal with the unique radiological and toxicological properties of DU. The Armed Forces Radiobiology Research Institute (AFRRI) is investigating health effects of embedded fragments of DU to determine whether current surgical fragment removal policies remain appropriate for this metal. These studies employ rodents implanted with DU pellets as well as cultured human cells exposed to DU... [ABSTRACT FROM AUTHOR]
Databáze: GreenFILE
Externí odkaz: