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- SKOG, K, et al.
(författare)
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EFFECT OF COOKING TEMPERATURE ON THE FORMATION OF HETEROCYCLIC AMINES IN FRIED MEAT-PRODUCTS AND PAN RESIDUES
- 1995
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 16:4, s. 861-867
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Tidskriftsartikel (refereegranskat)abstract
- Frequent consumers of meat have an increased risk of colorectal cancer and possibly also of breast, stomach, pancreas and urinary bladder cancer. Bacon, 'Falusausage', ground beef, meatballs, pork belly, pork chops and sliced beef account for more than one-third of the intake of fried meat of the population of Stockholm of age 50-75. These dishes were fried at four temperatures (150, 175, 200 and 225 degrees C) representing normal household cooking practices in Stockholm. Heterocyclic amines in these dishes were analysed using solid-phase extraction and HPLC. The heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo [4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were recovered. The formation of IQ was favoured by moderate cooking temperatures; IQ was detected in one meat sample cooked at 150 degrees C and in some pan residues. The yield of MeIQx, DiMeIQx and PhIP increased with the temperature. For several of the meat dishes, the content of heterocyclic amines in the pan residue was as large or larger than for corresponding piece of meat. The highest levels of MeIQx were 23.7 ng/g in the meat and 23.3 ng/g in the pan residue, Corresponding data for DiMeIQx were 2.7 and 4.1 ng/g and for PhIP 12.7 and 82.4 ng/g. The study leaves little doubt that mutagenic heterocyclic amines are ingested by the population of Stockholm, and added to previous epidemiological studies from the same area, the combined data are consistent with human carcinogenicity of heterocyclic amines, However, analytical epidemiological studies are needed before any statement on causality can be made.
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- Sundberg, Kathrin, et al.
(författare)
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Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons
- 1998
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 19:3, s. 433-436
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have identified allelic variants of the human glutathione transferase (GST) Pi gene and showed that the two different encoded proteins with isoleucine (GSTP1-1/I-105) or valine (GSTP1-1/V-105) at position 105, respectively, differ significantly in their catalytic activities with model substrates. Moreover, recent epidemiological studies have demonstrated that individuals differing in the expression of these allelic variants also differ in susceptibility to tumour formation in certain organs, including such in which polycyclic aromatic hydrocarbons (PAH) may be etiological factors. In the present study the catalytic efficiencies (kcat/Km) of these GSTP1-1 variants were determined with a number of stereoisomeric bay-region diol epoxides, known as the ultimate mutagenic and carcinogenic metabolites of PAH, including those from chrysene, benzo[a]pyrene and dibenz[a,h]anthracene. In addition, GSTP1-1 mutants in which amino residue 105 is alanine (GSTP1-1/A-105) or tryptophan (GSTP1-1/W-105) have been constructed and characterized. GSTP1-1/V-105 was found to be more active than GSTP1-1/I-105 in conjugation reactions with the bulky diol epoxides of PAH, being up to 3-fold as active towards the anti- and syn-diol epoxide enantiomers with R-absolute configuration at the benzylic oxiranyl carbon. Comparing the four enzyme variants, GSTP1-1/A-105 generally demonstrated the highest kcat/Km value and GSTP1-1/W-105 the lowest with the anti-diol epoxides. A close correlation was observed between the volume occupied by the amino acid residue at position 105 and the value of kcat/Km. With the syn-diol epoxides, such a correlation was observed with alanine, valine and isoleucine, whereas tryptophan was associated with increased kcat/Km values. The mutational replacement of isoleucine with alanine or tryptophan at position 105 did not alter the enantio selectivity of the GSTP1-1 variants compared with the naturally occurring allelic variants GSTP1-1/I-105 and GSTP1-1/V-105. Since the amino acid at position 105 forms part of the substrate binding site (H-site) the effect of increasing bulkiness is expected to cause restricted access of the diol epoxide and proper alignment of the two reactants for efficient glutathionylation. In conclusion, the present study indicates that individuals who are homozygous for the allele GSTP1* B (coding for GSTP1-1/V-105) display a higher susceptibility to malignancy because of other factors than a decreased catalytic efficiency of GSTP1-1/V-105 in the detoxication of carcinogenic diol epoxides of benzo[a]pyrene or structurally related PAH.
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