Effects of a lycopene-rich diet on spontaneous and benzo[a]pyrene-induced mutagenesis in prostate, colon and lungs of the lacZ mouse

doi:10.1016/S0304-3835(00)00705-9

Cancer Letters

Volume 164, Issue 1, 10 March 2001, Pages 1-6

https://doi.org/10.1016/S0304-3835(00)00705-9 Get rights and content

Abstract

Consumption of lycopene has been associated with reduced risk of prostate cancer. We have investigated the effects of lycopene, fed as a lycopene-rich tomato oleoresin (LTO) at two doses, on in vivo mutagenesis in prostate, colon, and lungs of lacZ mice. Both short-term benzo[a]pyrene (BaP)- induced and long-term spontaneous mutagenesis were monitored. Non-significant inhibition of spontaneous mutagenesis in prostate and colon was observed at the higher dose of LTO, and the observation of inhibition in colon was facilitated by an unusually high spontaneous mutagenesis rate. BaP-induced mutagenesis was slightly inhibited by LTO in prostate. However, enhancement of BaP-induced-mutagenesis was observed in colon and lung. These results indicate that any antimutagenic effects of LTO may be organospecific.

Introduction

The hydrocarbon carotenoid, lycopene, is found in relatively high concentrations in tomatoes and tomato products [1], [2]. It is a major serum carotenoid in humans [1], [2] and several, but not all epidemiological studies have reported inverse associations between estimated intake of tomato products and decreased incidence of prostate cancer (reviewed in [3]). One study reported an inverse association between prediagnostic serum lycopene and prostate cancer [4], but this was not seen in two other studies [5], [6]. There are also limited reports that lycopene consumption is inversely associated with cancers of the gastrointestinal tract [7], [8]. Lycopene is highly conjugated and is an effective scavenger of reactive oxygen species, and nitrogen dioxide radical [9], [10]. Thus, lycopene would be expected to be a potential protective agent against promutagenic DNA damage by reactive oxygen and probably other radical species and also against the possible tumor promoting effects of reactive oxygen species. Lycopene has been reported to inhibit formation of a number of experimental tumors (summarized in [11]) and was reported to inhibit spontaneous mutagenesis in cultured human colon cancer cells [12]. However, a lycopene-rich tomato oleoresin (LTO) had no effects on benzo[a]pyrene (BaP) + 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice [13] or mammary tumor induction by N-nitroso-N-methylurea in Sprague–Dawley rats [11]. Currently, there are no reports on the effect of lycopene on experimental tumorigenesis in prostate, which is its major proposed site of protection.

As experimental tumorigenesis is generally time and resource-consuming, a shorter term in vivo rodent assay has been developed to detect mutagenesis in any organ of the animal. The two major variations of the assay utilize lacZ or lacI mice [14], [15]. As mutations play a key role in carcinogenesis [16], the assay is sensitive to genotoxic initiators. However, since replication is necessary for the fixation of mutations, agents that enhance replication after DNA damage can also be distinguished in these assays [17]. The assay utilizes much smaller numbers of animals than carcinogenesis assays, and for carcinogen-induced mutations, can be completed in a much shorter period of time [14], [15].

In this study we have examined the effects of two levels of dietary supplementation of LTO on spontaneous mutagenesis and BaP-induced mutagenesis in three organs of lacZ mice. These organs include prostate and colon, where lycopene intake has been associated with reduced cancer incidence, and lung, a non-affected organ in experimental and epidemiological studies.

Section snippets

Chemicals

BaP, protease K and RNase A were purchased from Sigma Chemical Co. (St Louis, MO). Lycopene was provided as a 3.7% suspension (69 mM) in medium chain triglycerides from the Cognis Corp, (LaGrange, IL). In addition to lycopene the suspension contained 1.2% β-carotene, 0.3% phytofluene, 0.44% z-carotene, and 0.47% 2,6-cyclolycopene-1,5-diol. The concentrations and analyses of these components have been previously reported [18].

Animals

Male mice (Muta™Mouse, 6 weeks old) were purchased from Covance

Results

Addition of LTO to the diets of BaP-treated mice had organospecific effects on mutagenesis. BaP was mutagenic in prostate, although less so than in the in other organs. Mutagenesis in prostates from the LTO-treated groups was decreased compared to the BaP control group, and the decrease was dose-dependent. However, the differences in mutant fractions were not statistically significant. BaP, at the dose employed, was a potent mutagen in colon, and addition of LTO to the diet led to an increase

Discussion

The enhancing effects of lycopene on BaP-induced mutagenesis in colon and lung were somewhat unexpected based on previous experimental and epidemiological studies (see Section 1). In contrast, there was no enhancement of BaP-induced mutagenesis by LTO in prostate, but a non-significant dose-dependent decrease in mutagenesis was observed. The decrease was not statistically significant. However, the divergence in effects of lycopene in the organs examined suggests a possible specificity of

Acknowledgements

We thank the RAF of the American Health Foundation for expert technical assistance, Brian Pittman of the American Health Foundation for statistical analysis. C. Schweitzer and C. Potaczek of the Cognis Corporation, LaGrange IL, for kindly supplying the LTO gratis. Supported by Grant # CA76281 from the NIH: (NYU) and Cancer Centre Support Grant # CA17613 (AHF).

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Effects of a lycopene-rich diet on spontaneous and benzo[a]pyrene-induced mutagenesis in prostate, colon and lungs of the lacZ mouse

Abstract

Introduction

Section snippets

Chemicals

Animals

Results

Discussion

Acknowledgements

Arch. Biochem. Biophys.

Am. J. Clin. Nutr.

Cancer Lett.

Pharmac. Ther.

Mutat. Res.

The potential role of lycopene for human health

J. Am. Coll. Nutr.

Invited Commentary: Tomatoes, lycopene, and prostate cancer. How strong is the evidence?

Am. J. Epidemiol.

Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis

Cancer Res.

Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer

J. Natl. Cancer Inst.

Serum micronutrients and upper aerodigestive tract cancer

Cancer Epidemiol. Biomarkers Prev.