In vivo induction of sister-chromatid exchanges in liver and marrow cells by drugs requiring metabolic activation.

A highly sensitive method for the detection of in vivo induction of sister-chromatid exchange (SCE) has been developed in mice subjected to partial hepatectomy. SCE induction by either acetylaminofluorene (AAF) or cyclophosphamide, drugs requiring metabolic activation, is significantly greater in both regenerating liver and bone-marrow cells of partial hepatectomized animals than in marrow cells of unhepatectomized mice. These experiments have confirmed the ability of AAF, a well known mutagen-carcinogen, to induce SCE formation, even though the cytogenic effects of this drug on non-hepatectomized mice is very small. The in vivo system described has demonstrated the influence of the liver on drug-induced damage to extra-hepatic tissues. The procedures developed should facilitate the detection of drug-induced cytogenic damage and permit the comparison of inter-tissue differences in SCE induction with tissue-specific differences in drug-activation pathways.