Quantification of hormesis in anticancer-agent dose-responses.
Quantitative features of dose responses were analyzed for 2,189 candidate anticancer agents in 13 strains of yeast (Saccharomyces cerevisiae). The agents represent a diverse class of chemical compounds including mustards, other alkylating agents, and antimetabolites, inter alia. Previous analyses have shown that the responses below the toxic threshold were stimulatory and poorly predicted by a threshold dose-response model, while better explained by a hormetic dose-response model. We determined the quantitative features of the hormetic concentration-responses (n = 4,548) using previously published entry and evaluative criteria. The quantitative features that are described are: (1) the width of the concentration range showing stimulation above 10% of the control (mean of 5-fold), (2) the maximum stimulation of the concentration-responses (mean of 27% above the control), and (3) the width from the maximum stimulation to the toxicological threshold (mean of 3.7-fold). These results show that 52.5% of the 2,189 chemicals evaluated display hormetic concentration-responses in at least one of the 13 yeast strains. Many chemicals showed hormesis in multiple strains, and 24 agents showed hormesis in all 13 strains. The data are compared to previously reported quantitative features of hormesis based on published literature.
Nascarella
Marc A
MA
Department of Public Health, Environmental Health Sciences Division, University of Massachusetts-Amherst, Amherst, MA, USA. mnascarella@gradientcorp.com
Stanek
Edward J
EJ
Hoffmann
George R
GR
Calabrese
Edward J
EJ