Doubting Nongenotoxic Mechanisms of Renal Cancer: Comparing Apples and Oranges in the a2u-Globulin Hypothesis

Doubting accepted mechanisms in biology is not wrong per se, especially as the contrary would be the death blow to any form of advancement in research; however, doubting without good reason will consume precious energy and resources that could be spent on more fruitful and certainly more pressing matters in biological research. Contrary to good judgment, it appears that some individuals believe that any biological mechanism, however meticulously established and proven with hard data and despite being commonly accepted, should be doubted when the mechanism in question tends to reduce the conception of risk associated with chemicals. This doubt, however, does not appear to stem from hard factual data contradicting the mechanism, but rather from misinterpretation of available data and, in some instances, from the misquotation of the original investigators' conclusions. One recent example for doubting established and meticulously proven biological mechanisms is the ongoing discussion of the validity of the cc2u-globulin-associated male rat-specific mechanism of renal cancer induction and its ramifications for human health risk assessment. A unique database (certainly in its size and detail when compared to other databases with similar importance for human health concerns) on practically all aspects of this mechanism has been established by numerous scientists from many different unaffiliated laboratories, repeated scientific discussion sessions, several thorough reviews (1-8), and a workshop specifically devised to query all aspects of the data that support the mechanism in question (9). Despite this, some scientists, in an unfathomable quest to differ, choose to ignore the obvious and continue to doubt the validity of this mechanism by throwing up new hypotheses (10)