Synergistic or Antagonist Effects of Different UV Ranges Analyzed by the Combination Index: Application to DNA Photoproducts.

Abstract

Photobiological effects are known to greatly depend on the wavelength of the incident photons that define the nature of the activated chromophores. A growing number of experimental data show that considering the effect of complex light sources as a sum of the effects of monochromatic exposures can be misleading. Indeed, the combined exposure to several wavelength ranges may modulate photobiological responses or even induce novel processes. These observations are similar to a well-known topic in chemical toxicology: the nonadditivity of effects in mixtures where either antagonism or synergy are often observed. In the present work, we investigated whether a data analysis tool first developed for studying nonadditivity in mixtures of drugs, the combination index, could be applied to photobiological processes. We chose to work on the formation of UV-induced DNA photoproducts where additive, antagonist, and synergistic effects take place simultaneously. In addition to this application, we worked on the mathematical bases of the concept in order to broaden its applicability to phenomena exhibiting various dose-response patterns. We also addressed the question of the evaluation of the error on the determination of the combination index.