In vivo and in vitro genotoxicity of three antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine)

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Abstract
Three antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine) were found to be genotoxic in four in vivo or in vitro short-term test systems, a) In mice, a single ip administration of the LD50 of the three drugs caused a small but statistically significant increase over controls in DNA elution rate, ie, a modest amount of DNA fragmentation, in three of the four organs (liver, lung, kidney, and spleen) tested, DNA damage being absent in lung for hydralazine and endralazine and in liver for dihydralazine. Only for hydralazine DNA lesions were always repaired within 12 hr, in agreement with the constant lack of cumulative effects in mice given five successive daily doses. The rank of potencies was hydralazine< dihydralazinerecA recombination repair and the lexA post-replication repair (“SOS functions”) and, to a lesser extent, also the polymerase I mechanism, appeared to contribute to the specific DNA repair with all three drugs, while excision repair systems (uvrA and uvrB) did not appear to be involved.