In vitro assessment of oxidative stress and cytotoxicity in living dermal equivalents exposed to m-xylene.
Rogers-JV; Coleman-CA; Hull-BE; McDougal-JN
Toxicologist 2002 Mar; 66(1-S):162
Dermal exposure to volatile organic chemicals (VOCs) can lead to irritation, inflammation, and cytotoxicity in vivo. Using an improved in vitro exposure method for VOCs, we wanted to assess oxidative stress and cytotoxicity in dermal fibroblasts exposed to m-xylene. Dermal equivalents containing 2.5x105 cells were incubated for 1 or 4 hr in a m-xylene/culture medium mixture (range=0.5 to 11.5 g/ml m-xylene). Following exposure, cell viability (MTT assay and cellular LDH activity), cellular thiol levels, and endogenous catalase activity were measured. At 1 and 4 hr, cell viability decreased with increasing m-xylene concentration. The EC50 calculated using the MTT assay were 8.33 + 0.26 and 6.85 + 0.33 g m-xylene/g tissue at 1 and 4 hr, respectively. The EC50 at 4 hr was significantly lower (P<0.05) compared to the EC50 calculated from the 1 hr exposures. At 1 hr, the EC50 determined from measuring cellular LDH activity was 23.7 + 0.88 g m-xylene/g tissue. By 4 hr, the EC50 had decreased significantly (P<0.05) to 9.24 + 0.05 g m-xylene/g tissue. A temporal decrease in the levels of endogenous antioxidants (catalase and thiols) was also observed with increasing m-xylene concentration. Pretreatment of dermal equivalents with the antioxidant N-acetylcysteine significantly increased (P<0.05) cell viability. These results suggest oxidative stress may promote m-xylene-induced cytotoxicity in living dermal equivalents. Moreover, these VOC-induced cellular responses could ultimately be related to actual dermal exposure scenarios. (Supported by NIOSH/CDC and AFOSR/NL)
In-vitro-study; Stress; Cytotoxicity; In-vivo-study; Exposure-methods; Skin-exposure; Dermatitis; Dermatosis; Skin-diseases; Skin-disorders; Skin-irritants; Skin-lesions
Disease and Injury: Allergic and Irritant Dermatitis
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee
Wright State University, Dayton, Ohio