| 11922773 |
Charles GD, Gennings C, Zacharewski TR, Gollapudi BB, Carney EW: Assessment of interactions of diverse ternary mixtures in an estrogen receptor-alpha reporter assay. Toxicol Appl Pharmacol. 2002 Apr 1;180(1):11-21.
This study used an MCF-7 cell based ER-alpha reporter gene assay to assess chemical interactions within the following ternary mixtures: (1) three synthetic pesticides, methoxychlor (MXC), o,p-DDT, and dieldrin; (2) three polyaromatic hydrocarbons, benzo [a] pyrene (BAP), 1,2-benzanthracene (BENZ), and chrysene (CHRY); and (3) an endogenous estrogen, [17beta-estradiol, (E (2))]; a phytoestrogen, genistein (GEN); and a synthetic estrogen, o,p-DDT. A full factorial design in which four concentrations of each chemical were assessed in all possible combinations (64 treatment groups) was utilized. In addition, mixtures were tested in both a low range (concentrations near the individual chemical response thresholds) and a high range ( approximately 2-10x higher) experiment. A response surface was estimated using a nonlinear mixed model, and the cumulative response in each mixture was evaluated for departure from additivity. The mixture of E (2), GEN, and DDT exhibited antagonistic interactions (p < 0.001) in both concentration ranges. However, specific interactions between E (2)/GEN and E (2)/DDT differed between the low and high range concentrations. The BAP/BENZ/CHRY mixture did not depart significantly from additivity (p = 0.66) in either concentration range, although response levels were generally low. The MXC/DDT/dieldrin mixture did not depart significantly from additivity in either the high (p = 0.065), or low dose range (p = 0.506), with generally minimal responses dominated by MXC and DDT. This methodology has allowed for a rigorous statistical evaluation of potential departures from additive interactions in endocrine active mixtures. In no case was a significantly greater-than-additive (synergistic) interaction observed. |
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