Cancer Letters

Cancer Letters

Volume 152, Issue 2, 1 May 2000, Pages 169-173
Cancer Letters

Lipid peroxidation status, somatic mutations and micronuclei in peripheral lymphocytes: a case observation on a possible interrelationship

https://doi.org/10.1016/S0304-3835(00)00332-3Get rights and content

Abstract

A controlled dietary study was conducted in healthy female volunteers and reported elsewhere [1]. In a subset of samples four different biomarkers were analyzed: plasma malondialdehyde (MDA) levels and urinary 8-isoprostaglandin-F were measured as markers for lipid peroxidation. The frequency of hprt (hypoxanthine guanine phosphoribosyl transferase) mutants and micronuclei in peripheral blood lymphocytes were analyzed as indicators of genotoxic effects. One of the ten individuals showed extremely high background levels in all of the four endpoints measured. This case observation raises the possibility that life style factors and dietary habits affect the level of DNA reactive lipid peroxidation products, which in turn increase mutagenic and cytogenetic effects. A possible association between these biomarkers, particularly in relation to dietary fat intake and antioxidant status, should now be studied in a larger trial.

Introduction

Lipid peroxidation (LPO) products are regarded as one of the major sources for endogenous genotoxic compounds. The toxicological significance of this process has been linked to spontaneous mutagenesis and carcinogenesis [2]. The main precursors of LPO-products are derived from dietary polyunsaturated fatty acids and from arachidonic acid present in membrane lipids. As a consequence, LPO might be influenced by individual dietary habits. Within a larger trial on dietary fat-related adverse effects [1], a subset of ten female volunteers was analyzed for different biomarkers at two repeated time points: Plasma malondialdehyde (MDA) levels and urinary 8-isoprostaglandin-Fwere measured as markers for LPO, while hprt (hypoxanthine guanine phosphoribosyl transferase) mutants and micronuclei frequencies in peripheral blood lymphocytes were analyzed as indicators of genotoxic effects. This pilot study revealed a good reproducibility between blood samples of the same individual taken at two different time points. Here, we report a case observation, which suggests an association between the LPO status on one hand and genotoxicity in lymphocytes on the other.

Section snippets

Subjects and study design

The data presented are derived from a larger controlled nutritional intervention trial carried out at the University of Helsinki, Finland as described in detail by Freese et al. [1]. Ten healthy, non-smoking female volunteers with normal body weight (body mass index 19.2–28.4 kg/m2) and a mean age of 34 (26–45) years consumed a controlled diet containing 27 energy% as fat, with 8% from saturated, 9% from monounsaturated and 10% from polyunsaturated fatty acids (mainly linoleic acid from

Results and discussion

Four different biomarkers, i.e. plasma MDA levels, urinary 8-iso-PGF and frequencies of hprt mutants and micronuclei in peripheral blood lymphocytes, were studied in ten female volunteers at two different time points being 4 weeks apart. Individual results are shown in Fig. 1. In nine out of ten subjects the number of isolated lymphocytes were sufficient for hprt mutation analysis by T-cell cloning (value for participant ‘H’ missing). The cloning efficiencies under non-selective conditions

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