Formation of Interstrand DNA Cross-Links by Bis-(2-chloroethyl)Sulfide (BCES): A Possible Cytotoxic Mechanism in Rat Keratinocytes

Author： Lin P. Vaughan F.L. Bernstein I.A.

Publisher： Elsevier

ISSN： 0006-291X

Source： Biochemical and Biophysical Research Communications, Vol.218, Iss.2, 1996-01, pp. : 556-561

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Abstract

Interstrand cross-links in the DNA of epidermal basal keratinocytes may be responsible for cell death and consequent vesication in skin exposed to BCES. The formation of cross-links and cytotoxicity were compared when cells in primary monolayer cultures of rat epidermal keratinocytes, synchronized at the G1/S boundary or in the G1 phase of the cell cycle, were exposed to BCES. The dose-responsive formation of cross-links, measured with an ethidium bromide-fluorescence assay, was determined immediately after exposure of cells at either position of the cycle. At 24 hr post-exposure, the level of cross-links in cells exposed at the G1/S boundary had not decreased significantly and was still dose-dependent. However, cells exposed in the G1 phase showed a major decrease in cross-links. Formation of interstrand DNA cross-links appears to be related to the mustard's cytotoxicity.