Cancer AOP Workgroup. National Health and Environmental Effects Research Laboratory, Office of Research and Development, Integrated Systems Toxicology Division, US Environmental Protection Agency, Research Triangle Park, NC. Corresponding author for wiki entry (email@example.com)
This putative adverse outcome pathway (AOP) outlines potential key events leading to a tumor outcome in standard carcinogenicity models. This information is based largely on modes of action described previously in cited literature sources and is intended as a resource template for AOP development and data organization. Presentation in this Wiki does not indicate EPA acceptance of a particular pathway for a given reference agent, only that the information has been proposed in some manner. In addition, this putative AOP relates to the model species indicated and does not directly address issues of human relevance.
Sex: This AOP applies to males only (Swenberg, 1993).
Life stages: The relevant life stages for this AOP are reproductively mature adults. Alpha2u-microglobulin is found in the urine of female and sexually immature rats at concentrations that are less than 1/100 that found in young adult males (Vandoren et al 1983, Ekstrom et al 1984, as cited in Swenberg 1993). Hepatic synthesis accounts for most of the o2u in male rats, with synthesis beginning at the onset of sexual maturity and increasing to 20 weeks of age, after which it plateaus and then begins to decline with increasing age (Roy et al 1983, as cited in Swenberg 1993).
Taxonomic: The taxonomic applicability domain of this AOP is rats, Rattus norvegicus (Swenberg, 1993).
Swenberg, J. A. (1993). Alpha 2u-globulin nephropathy: review of the cellular and molecular mechanisms involved and their implications for human risk assessment. Environ Health Perspect, 101 Suppl 6, 39-44.