Bone marrow injury induced via oxidative stress in mice by inhalation exposure to formaldehyde.

Abstract

Formaldehyde, a ubiquitous environmental pollutant has been classified as a human leukemogen. However, toxicity of formaldehyde in bone marrow, the target site of leukemia induction, is still poorly understood. To investigate bone marrow toxicity (bone marrow pathology, hematotoxicity) and underlying mechanisms (oxidative stress, inflammation, apoptosis) in formaldehyde-exposed mice. Male Balb/c mice were exposed to formaldehyde (0, 0.5, and 3.0 mg/m(3)) by nose-only inhalation for 8 hours/day, over a two week period designed to simulate a factory work schedule, with an exposure-free "weekend" on days 6 and 7, and were sacrificed on the morning of day 13. Counts of white blood cells, red blood cells and lymphocytes were significantly (p<0.05) decreased at 0.5 mg/m(3) (43%, 7%, and 39%, respectively) and 3.0 mg/m(3) (52%, 27%, and 43%, respectively) formaldehyde exposure, while platelet counts were significantly increased by 109% (0.5 mg/m(3)) and 67% (3.0 mg/m(3)). Biomarkers of oxidative stress (reactive oxygen species, glutathione depletion, cytochrome P450 1A1 and glutathione s-transferase theta 1 expression), inflammation (nuclear factor kappa-B, tomour necrosis factor alpha, interleukin-1 beta), and apoptosis (activity of cysteine-aspartic acid protease 3) in bone marrow tissues were induced at one or both formaldehyde doses mentioned above. Exposure of mice to formaldehyde by inhalation induced bone marrow toxicity, and that oxidative stress, inflammation and the consequential apoptosis jointly constitute potential mechanisms of such induced toxicity.