Medical Research and Evaluation Facility and Studies Supporting the MedicalChemical Defense Program. A Comparison of the Biochemical Changes Produced by Vesicating and Non-Vesicating Alkylating Agents in Normal Human Epidermal Keratinocytes

摘要

Task 91-23 was conducted for the U.S. Army Medical Research Institute of ChemicalDefense (USAMRICD) to compare alterations in selected biochemical endpoints using human epidermal keratinocytes (HEK) exposed in vitro to either non-vesicating (e.g., cisplatin) or vesicating (e.g., sulfur mustard; MD) alkylating agents. These data may provide insight into the biochemical mechanism(s) uniquely associated with tissue vesication. Preliminary in vivo experiments used three vesicating and three non-vesicating alkylating agents to confirm vesication potential by examining microblister formation in the hairless guinea pig (HGP). The three vesicating, alkylating agents selected were MD (positive control), mechlorethamine (nitrogen mustard; HN2), and chloroethylethyl sulfide (CEES). The three non-vesicating, alkylating agents selected were cisplatin, meiphalan, and thiotepa.