The studied molecules are : Range : 5 to 100 µMDADS (diallyl sulfide) DADSO (allicin) SAC (S-allyl cystein) AM (allyl mercaptan) Anti-genotoxicity studies.

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Presentation transcript:

The studied molecules are : Range : 5 to 100 µMDADS (diallyl sulfide) DADSO (allicin) SAC (S-allyl cystein) AM (allyl mercaptan) Anti-genotoxicity studies in HepG2 cells Objectives : to assess if garlic compounds prevent DNA alterations induced by mutagenic compounds in a human cell line. DNA alterations are measured using the comet test which has been presented in the last meeting. Anne-Marie le Bon et al.

Two different protocols are scheduled in order to test different mechanisms of action:  Pre-treatment : cells are treated with the garlic compound first then with the pro-mutagen The tested hypothesis are inhibition or induction of xenobiotic metabolizing enzymes by garlic compounds Garlic compoundPro-mutagen  Co-treatment : cells are treated with both the garlic compound and the direct-acting mutagen at the same time The tested hypothesis is scavenging of mutagenic compounds by garlic compounds Garlic compound + mutagen 3 mutagens, which are activated through different mechanisms have been selected for this study : benzopyrene, aflatoxin B1 and nitrosodimethylamine. They are activated by P450 1A, 3A and 2E1, respectively. 3 mutagens, which act through different mechanisms have been selected for this study : hydrogen peroxide, methyl methane sulfonate, 4-nitrosoquinoline oxide.

Preliminary results DADSDADSO SACAM Nitrosodimethyl- amine n.d. Aflatoxin B1  ?? Benzopyrene  ? Pre-treatment studies  : inhibition of the genotoxicity ? : inconclusive results. Additionnal experiments are needed. n.d. : not determinated Comments -This study is currently under investigation. Therefore these results must be taken with caution. - Nevertheless, the preliminary results show that DADS and AM are able to inhibit the genotoxicity of benzopyrene and aflatoxin B1. - The effects of DADSO and SAC are not yet known. We need to do more experiments. - The antigenotoxic properties of garlic compounds against nitrosodimethylamine could not been assessed because we did not observed a genotoxic effect of this compound in our cell line. We suppose that our cell line does not possess P450 2E1 which is involved in activation of nitrosamine. We will use another batch of HepG2 cell.

Preliminary results - 2 DADSDADSO SACAM Hydrogen peroxide  ?? 4-Nitrosoquinoline oxide ???? Methyl methane sulfonate  ?? Co-treatment studies  : inhibition of the genotoxicity - : no effect ? : inconclusive results. Additionnal experiments are needed. Comments - DADS, DADSO and SAC seem to be able to inhibit the genotoxicity of direct-acting mutagens but additionnal experiments are needed to confirm these preliminary results.

CONCLUSIONS These preliminary results suggest that garlic compounds can prevent DNA alterations induced by chemicals in a human cell line. But we have to repeat the experiments before providing definitive results. Final results will be available before the end of this year.