Four aliphatic
epoxides, 1-naphthyl glycidyl
ether (NGE),
1-naphthylpropylene oxide (NPO),
4-nitrophenyl glycidyl
ether (NPGE), 3,3,3-trichloropropylene
oxide (TCPO) and two of their precursors, 1-allylnaphthalene (AN) and 3,3,3-trichloropropylene (TCP), were selected for
DNA strand-break analysis in liver in vivo with mice. The four
epoxides selected were among the most mutagenic aliphatic
epoxides in our previous structure-mutagenicity studies with the Ames test and had been evaluated for their in vivo genotoxicity as measured by sister-chromatid exchange (SCE) and
chromosome aberrations (CA). A significant increase in the percentage of unwound
DNA was observed at a 4-h exposure time for all the compounds at high doses except for AN. TCPO, the least genotoxic compound in bone marrow, had the greatest liver toxicity after 1-h exposure while NGE showed the most toxicity after 6 h. As might be expected from their corresponding
epoxides, AN but not TCP exhibited significant SCE activity in the bone marrow of mice. This study reemphasizes the importance of evaluating the stability of direct-acting
alkylating agents in comparing test results and in establishing the relative order of genotoxicity for such compounds.