DNA strand breaks in liver for four aliphatic epoxides in mice.
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.
Giri
A K
AK
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Messerly
E A
EA
Chakraborty
P K
PK
Hooberman
B H
BH
Sinsheimer
J E
JE
D000818:Animals; D004249:DNA Damage; D004852:Epoxy Compounds / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009153:Mutagens; D012854:Sister Chromatid Exchange
D004852:Epoxy Compounds; D009153:Mutagens