Cancer biology and hormesis: human tumor cell lines commonly display hormetic (biphasic) dose responses

This article assesses the nature of the dose-response relationship of human tumor cell lines with a wide range of agents including antineoplastics, toxic substances (i.e., environmental pollutants), nonneoplastic drugs, endogenous agonists, and phyto-compounds. Hormetic-like biphasic dose responses were commonly reported and demonstrated in 136 tumor cell lines from over 30 tissue types for over 120 different agents. Quantitative features of these hormetic dose responses were similar, regardless of tumor cell line or agent tested. That is, the magnitude of the responses was generally modest, with maximum stimulatory responses typically not greater than twice the control, while the width of the stimulatory concentration range was usually less than 100-fold. Particular attention was directed to possible molecular mechanisms of the biphasic nature of the dose response, as well as clinical implications in which a low concentration of chemotherapeutic agent may stimulate tumor cell proliferation. Finally, these findings further support the conclusion that hormetic dose responses are broadly generalizable, being independent of biological model, endpoint measured, and stressor agent, and represent a basic feature of biological responsiveness to chemical and physical stressors.