Absence of genotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) and its potential chemoprevention against DNA damage using in vitro and in vivo assays.

The chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one), or 2HMC, displays antileishmanial, antimalarial, and antioxidant activities. The aim of this study was to investigate the cytotoxic, genotoxic, mutagenic, and protective effects of 2HMC using the Ames mutagenicity test, the mouse bone marrow micronucleus test, and the comet assay in mice. In the assessment using the Ames test, 2HMC did not increase the number of His+ revertants in Salmonella typhimurium strains, demonstrating lack of mutagenicity. 2HMC showed no significant increase in micronucleated polychromatic erythrocyte frequency (MNPCE) in the micronucleus test, or in DNA strand breaks using the comet assay, evidencing absence of genotoxicity. Regarding cytotoxicity, 2HMC exhibited moderate cytotoxicity in mouse bone marrow cells by micronucleus test. 2HMC showed antimutagenic action in co-administration with the positive controls, sodium azide (SA) and 4-nitroquinoline-1-oxide (4NQO), in the Ames test. Co-administered and mainly pre-administered with cyclophosphamide (CPA), 2HMC caused a decrease in the frequency of MNPCE using the micronucleus test and in DNA strand breaks using the comet assay. Thus, 2HMC exhibited antimutagenic and antigenotoxic effects, displaying a DNA-protective effect against CPA, SA, and 4NQO carcinogens. In conclusion, 2HMC presented antimutagenic, antigenotoxic and moderate cytotoxic effects; therefore it is a promising molecule for cancer prevention

Synthetic route of chalcone 2HMC (1).

<p>Reagents and conditions: (a) 50% NaOH (w/w), EtOH, 12 h (room temperature).</p

Effects of treatments with different doses of the chalcone (<i>E</i>)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) (2HMC) on the frequency of micronucleated polychromatic erythrocytes (MNPCE) and polychromatic/normochromatic erythrocyte ratio (PCE/NCE) in bone marrow cells of mice.

<p>Effects of treatments with different doses of the chalcone (<i>E</i>)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) (2HMC) on the frequency of micronucleated polychromatic erythrocytes (MNPCE) and polychromatic/normochromatic erythrocyte ratio (PCE/NCE) in bone marrow cells of mice.</p

Means ± standard deviation (SD) of histidine revertant colonies (obtained from three independent experiments carried out in triplicate), mutagenic index (MI), and inhibition percentage of mutagenicity (IP) for two tester strains of <i>Salmonella typhimurium</i>, TA98 and TA100, after treatment with different doses of the chalcone (<i>E</i>)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) (2HMC).

<p>Means ± standard deviation (SD) of histidine revertant colonies (obtained from three independent experiments carried out in triplicate), mutagenic index (MI), and inhibition percentage of mutagenicity (IP) for two tester strains of <i>Salmonella typhimurium</i>, TA98 and TA100, after treatment with different doses of the chalcone (<i>E</i>)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) (2HMC).</p

Assessment of the genotoxic and antigenotoxic activities of the chalcone (<i>E</i>)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) (2HMC) at different doses in mice bone marrow cells using the comet assay estimated by the parameter %DNA in tail.

<p>DMSO, dimethylsulfoxide (negative control); CPA, cyclophosphamide (50 mg/kg BW) (positive control). ANOVA and the Tukey’s test: *significant compared to the positive control (<i>p</i> < 0.05). Groups 3 and 4, treated only with 2HMC, were compared to the negative control. Groups 5, 6, 7, 8, 9, and 10, co-, pre-, or post-treated were compared to the positive control.</p

Protective Effects of Silymarin and Silibinin against DNA Damage in Human Blood Cells

Silymarin (SM), a standardized extract derived from Silybum marianum (L.) Gaertn, is primarily composed of flavonolignans, with silibinin (SB) as its major active constituent. The present study aimed to evaluate the antigenotoxic activities of SM and SB using the alkaline comet assay in whole blood cells and to assess their effects on the expression of genes associated with carcinogenesis and chemopreventive processes. Different concentrations of SM or SB (1.0, 2.5, 5.0, and 7.5 mg/ml) were used in combination with the DNA damage-inducing agent methyl methanesulfonate (MMS, 800 μM) to evaluate their genoprotective potential. To investigate the role of SM and SB in modulating gene expression, we performed quantitative real-time PCR (qRT-PCR) analysis of five genes that are known to be involved in DNA damage, carcinogenesis, and/or chemopreventive mechanisms. Treatment with SM or SB was found to significantly reduce the genotoxicity of MMS, upregulate the expression of PTEN and BCL2, and downregulate the expression of BAX and ABL1. We observed no significant changes in ETV6 expression levels following treatment with SM or SB. In conclusion, both SM and SB exerted antigenotoxic activities and modulated the expression of genes related to cell protection against DNA damage