Trans-4-hydroxy-2-nonenal, an aldehydic lipid peroxidation product, lacks genotoxicity in lacI transgenic mice

In order to cast light on the significance of lipid peroxidation products f or carcinogenesis, the lad mutant frequency (MF), micronucleus induction an d cell proliferation were analyzed in lad transgenic mice treated with tran s-4-hydroxy-2-nonenal (HNE), a typical example. Male mice were ip injected with HNE at doses of 0, 5 or 50 mg/kg bw and 48 h thereafter, peripheral bl ood was collected for analyzing micronucleus induction, After 14 days, the mice were sacrificed to allow tissue sampling for examination of lad MF and cell proliferative activity. Sixty percent of the mice given 50 mg/kg HNE died within 5 days after the treatment, but no other mortalities were obser ved. Histopathologically, marked pulmonary hemorrhage was found in the 50 m g/kg HNE group mice that survived until day 14. Immunohistochemically, HNE- modified proteins were detected in their alveolar macrophages, The HNE trea tment did not increase lacI MF in the liver, kidney and lung and no signifi cant increase in micronucleus induction or cell proliferation in major orga ns was found in either treatment. Moreover, no tumors developed in the 5 mg /kg HNE-treated mice which survived until week 78. Our results thus indicat e that HNE lacks in vivo genotoxicity in lad transgenic mice even when leth al doses are applied. (C) 2000 Elsevier Science Ireland Ltd, All rights res erved.