Formation of interstrand DNA cross-links by bis-(2-chloroethyl)sulfide (BCES): a possible cytotoxic mechanism in rat keratinocytes.
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 phase showed 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.
Lin
P
P
Department of Environmental and Industrial Health, University of Michigan, Ann Arbor 48109, USA.
Vaughan
F L
FL
Bernstein
I A
IA
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D003879:Dermatologic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D009151:Mustard Gas / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors; D051381:Rats
D003432:Cross-Linking Reagents; D003879:Dermatologic Agents; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D016590:Aphidicolin; D004247:DNA; D009151:Mustard Gas