Dietary intake of meat and meat-derived heterocyclic aromatic amines and their correlation with DNA adducts in female breast tissue.

It was the aim of this study to examine the association of the consumption of meat in general, meat prepared by different cooking methods and the dietary intake of heterocyclic aromatic amines (HCA) with the level of DNA adducts in the breast tissue of women undergoing reduction mammoplasty. Dietary intake of meat and HCA were assessed via questionnaire in 44 women undergoing reduction mammoplasty. DNA adduct analysis in breast tissue was performed by (32)P-postlabelling analysis.

Formation of mutagenic heterocyclic aromatic amines in fried pork from Duroc and Landrace pigs upon feed supplementation with creatine monohydrate.

Heterocyclic aromatic amines (HAA) have been shown to induce tumours at various organ sites in experimental animal studies and high levels of dietary intake of HAA have been associated with increased cancer risk in humans. These HAA are formed in meat upon heating from precursors such as amino acids, reducing sugars and creatine or creatinine. Groups of ten Duroc and ten Landrace pigs received feed supplemented with creatine monohydrate (CMH) for five days prior to slaughter at dose levels of 12.

Modulation of cytochrome P450 1A1 by food-derived heterocyclic aromatic amines.

A short-term effect of a meal of fried meat is a postprandial induction of hepatic and intestinal cytochrome P450 activity. In order to identify the components responsible for this effect we investigated the potency of food derived genotoxic heterocyclic aromatic amines (HA) to induce CYP1A1 in vitro. In two cell lines, the rat hepatoma cell line H4IIE and the human breast cancer cell line MCF-7, we investigated 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAC), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and Harman representing the different classes of HA at concentrations from 10(-8) to 10(-4) M.

Syntheses of DNA adducts of two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and 2-amino-9H-pyrido[2,3-b]indole (AalphaC) and identification of DNA adducts in organs from rats dosed with MeAalphaC.

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (AalphaC) are mutagenic and carcinogenic heterocyclic amines formed during ordinary cooking. MeAalphaC and AalphaC are activated to mutagenic metabolites by cytochrome P450-mediated N-oxidation to the corresponding N2-OH derivatives. The proximate mutagenic N2-OH derivatives of MeAalphaC and AalphaC did not react with deoxynucleosides or DNA.

In vitro evolution of RNA aptamers recognizing carcinogenic aromatic amines.

The modification of cellular DNA by environmental substances is thought to be a crucial event in chemical induced carcinogenesis. Among the environmental carcinogens, aromatic amines are known for the fact that they can induce several types of cancers through the formation of so-called DNA adducts. We took advantage of the potential of the SELEX method to select for highly specific RNA ligands that recognize specific genotoxic aromatic amines.

Analyses of bulky DNA adduct levels in human breast tissue and genetic polymorphisms of cytochromes P450 (CYPs), myeloperoxidase (MPO), quinone oxidoreductase (NQO1), and glutathione S-transferases (GSTs).

Environmental carcinogens are converted into DNA-reactive metabolites by phase I and phase II enzymes that are involved in the activation and detoxification of xenobiotics. Several of these enzymes display genetic polymorphisms that alter their activity leading to individual variation in DNA damage levels and thus cancer susceptibility. We investigated the relationship between DNA adduct levels and genetic polymorphisms in key enzymes of chemical carcinogenesis: CYP1A1, CYP1A2, GSTT1, GSTM1, GSTP1, NQO1 and MPO.