Alkylation of deoxyguanosine by the sesquiterpene lactone hymenoxon.

Hymenoxon, a toxic sesquiterpene lactone found in the ruminant forage plant Hymenoxys odorata, binds deoxyguanosine in a cell-free system, and forms adducted guanine residues in sheep lymphocyte DNA. Mitogen-stimulated DNA synthesis in lymphocytes was inhibited by hymenoxon at concentrations greater than 100 microM. Unscheduled DNA synthesis in lymphocytes was initiated by hymenoxon concentrations exceeding 50 microM, and inhibited by concentrations above 100 microM. We describe an HPLC method which separates unmodified hymenoxon and deoxyguanosine from the hymenoxon-deoxyguanosine adduct, and allows the quantitation of adducts in hymenoxon-treated cells.