Cell death and production of reactive oxygen species by murine macrophages after short term exposure to phthalates.
The effects of four phthalates, i.e., di-2-ethylhexyl phthalate (DEHP), butyl benzyl phthalate (BBP), dibutyl phthalate (DBP) and diisobutyl phthalate (DIBP) on necrotic and apoptotic cell death, and production of reactive oxygen species (ROS) were studied on mouse macrophage cell line RAW 264.7. All the phthalates caused negligible and non-dose-dependent ROS production compared to control experiment. DEHP and BBP did not cause significant necrotic nor apoptotic cell death at any of the studied doses. Both DIBP and DBP caused dose-dependent necrotic cell death at the two highest concentrations (100 microM and 1 mM). Both doses (500 microM and 1 mM) of DIBP increased apoptosis by 31- and 60-fold, respectively, whereas the increase in apoptotic cell death caused by DBP was only two and fourfold, that however, was not statistically significant. In conclusion, DIBP caused a substantially different apoptotic cell death effect on murine macrophages from the three other phthalates, and this effect was not related to ROS production. Thus, toxicological and health risks of DIBP and DBP should be assessed separately in the future.
Naarala
J
J
University of Kuopio, Department of Environmental Science, Kuopio, Finland.
Korpi
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010795:Phthalic Acids / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
D010795:Phthalic Acids; D017382:Reactive Oxygen Species