Sulphur mustard induced DNA damage in mice after dermal and inhalation exposure.
Sulphur mustard (SM) is a chemical warfare agent of the blistering agent category for which there is still no effective therapy. SM, being a strong electrophile, readily reacts with a wide range of cellular macromolecules including DNA, RNA and protein. Since the main intoxication routes for SM are inhalation and dermal penetration, in the present study we have exposed female mice to different concentrations of SM by dermal and inhalation exposures and estimated the DNA damage in different organs viz., liver, lung, spleen and thymus. SM was applied at 38.7, 77.4, 154.7 mg/kg body weight, on the hair-clipped skin (dermal exposure) equivalent to 0.25, 0.5 and 1.0 of the LD50. Inhalation exposure was carried out at 10.6, 21.2 and 42.3 mg/m3 for 1 h duration equivalent to 0.25, 0.5 and 1.0 LC50. SM induced a dose-dependent DNA damage in all the organs except the lung in dermal exposure. Similarly the inhalation exposure resulted in dose- and time-dependent effect in all the organs including lung. By both routes of exposure liver was the most affected organ followed by spleen, thymus and lung in decreasing order. The quantitative data were corroborated by qualitative analysis of DNA on agarose gel electrophoresis. The genomic DNA analysis of the organs had revealed random nuclear DNA fragmentation resulting in a 'smear' typical of necrotic form of cell death. Since DNA damage is not reversible especially in liver, this can be used as a marker for SM exposure through either the dermal or inhalation route.
Lakshmana Rao
P V
PV
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India. drde@gwr1.dot.net.in
Vijayaraghavan
R
R
Bhaskar
A S
AS
D000280:Administration, Inhalation; D000287:Administration, Topical; D000818:Animals; D015415:Biomarkers; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004247:DNA / Q000032:analysis; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D005260:Female; D051379:Mice; D009151:Mustard Gas / Q000008:administration & dosage / Q000633:toxicity*; D012867:Skin / Q000473:pathology; D013997:Time Factors
D015415:Biomarkers; D002619:Chemical Warfare Agents; D004247:DNA; D009151:Mustard Gas