Prevention of 1,2-dibromo-3-chloropropane (DBCP)-induced kidney necrosis and testicular atrophy by 3-aminobenzamide.

ABSTRACT

The poly(ADP-ribosyl)transferase inhibitor, 3-aminobenzamide (3-ABA), reduced morphological evidence of 1,2-dibromo-3-chloropropane (DBCP)-induced DNA damage determined by alkaline elution. The DBCP plasma, kidney, and testis tissue doses determined between 1 and 8 hr after a single intraperitoneal injection were somewhat higher with than without 3-ABA pretreatment. Furthermore, the amount of DBCP metabolites covalently bound to macromolecules was reduced to about 20-30 percent of control, indicating that 3-ABA may have an effect on the formation/detoxication of reactive DBCP metabolites. Inhibitors of replicative DNA synthesis such as hydroxyurea or stimulation of DNA replication by nephrectomy did not affect the cytotoxicity, neither did inhibitors of DNA repair such as beta-cytosine arabinoside and beta-lapachone.