The Alternaria toxins
alternariol (AOH) and
alternariol monomethyl ether (
AME) have been reported previously to act as activators of the
aryl hydrocarbon receptor (AhR) in murine
hepatoma cells, thus enhancing the expression of
cytochrome P450 (CYP) 1A
monooxygenases. Concomitantly, both benzopyrones represent substrates of CYP1A, giving rise to catecholic metabolites. The impact of AOH and
AME on CYP1A expression in human cells of different tissue origin colon (HT29), esophagus (KYSE510), liver (HepG2) and their effects on cell viability, generation of
reactive oxygen species (ROS) and
DNA integrity were investigated. ROS production was induced by both
mycotoxins in all cell lines with AOH exhibiting the highest potency in esophageal cells concomitant with the most prominent CYP1A induction level. Of note,
altertoxin-II (ATX-II), the more potent
DNA-damaging
mutagen formed by Alternaria alternata, induces CYP1A even at significant lower concentrations. AhR-
siRNA knockdown in human esophageal cells supported the hypothesis of AhR-mediated
CYP1A1 induction by AOH. However, DNA damage was minor at CYP1A1-inducing AOH concentrations. AhR-depletion did not affect the
DNA-damaging properties of AOH indicating no substantial impact of AhR in this regard. However, in combination with
xenobiotics prone to metabolic activation by CYP1A the induction of CYP1A by Alternaria toxins deserves further attention.