4-Hydroxynonenal (HNE), one of the major products of lipid peroxidation, has been demonstrated to induce genotoxic effects in the micromolar range. HNE has too structural domains, a lipophilic tail and a polar head with three functional groups: the
aldehyde and hydroxy groups and the trans CC double bond. To evaluate their relative importance, the genotoxic effects of HNE were compared with those of the homologous
aldehydes 4-hydroxyhexenal and
4-hydroxyundecenal (different lengths of the lipophilic tail), and the analogous
aldehydes 2-trans-nonenal (lacking the
OH group) and
nonanal (lacking the
OH group and the trans CC double bond). This investigation was carried out on primary cultures of adult rat hepatocytes in order to further determine the influence of biotransformation- and/or detoxification reactions. A 3-h treatment with HNE induces statistically significant levels of SCE at concentrations > or = 0.1 microM, micronuclei at concentrations > or = 1 microM and
chromosomal aberrations at a concentration of 10 microM. Compared to HNE the homologous
aldehydes induced a significant genotoxic effect at higher concentrations. Statistically significant increases in SCE frequency were obtained at concentrations > or = 1 microM for
4-hydroxyundecenal and at a concentration of 10 microM for
4-hydroxyhexenal. The induction of
chromosomal aberrations was significantly elevated at concentrations of > or = 10 microM and 10 microM for
4-hydroxyhexenal and
4-hydroxyundecenal, respectively. Except for a
4-hydroxyhexenal concentration of 1 microM, both
aldehydes did not induce statistically significant levels of micronuclei. The HNE analogous
aldehydes 2-trans-nonenal and
nonanal induced statistically significant frequencies of SCE at concentrations of > or = 1 microM (
nonanal) and > or = 10 microM (2-trans-nonenal). No significant induction of
chromosomal aberrations or micronuclei could be demonstrated. The structure of the
aldehydes investigated appears to influence the cyto- and genotoxic potential in the following ways. (1) The length of the lipophilic tail has no influence on
chromosomal aberration induction, but appears to determine the yield of SCE and micronuclei, and the cytotoxic potential. (2) The lack of the
OH group (2-trans-nonenal) reduces the SCE-inducing potential of the
aldehyde shifting the dose-effect curve to higher concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)