Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue
Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue
How to find us email us Work suggesting that some food substances may be linked to prostate cancer formation: current research is examining ways of reversing this and detailing possible pathways. The full paper is published in Carcinogenesis Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue Epidemiological evidence suggests a link between meat consumption and prostate cancer. In this study, benign prostatic hyperplasia tissues, obtained by transurethral resection or radical retropubic prostatectomy from UK-resident individuals (n=18), were examined for CYP1 expression and for their ability, in short term organ culture, to metabolically activate carcinogens found in cooked meat. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of CYP1 expression detected CYP1A2 mRNA transcripts in the prostates of 4/4 individuals, as well as mRNA transcripts from CYP1A1 and CYP1B1. The compounds tested for metabolic activation were 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 500mM, n=9) and its metabolite N-hydroxy PhIP (20mM, n=8), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 500mM, n=6) and benzo[a]pyrene (B[a]P, 50mM, n=5). After incubation (PFMR medium, 22h, 37°C) DNA was isolated from tissue fragments and DNA adducts were detected and quantified by 32P-postlabelling analysis. DNA adduct formation was detected in all samples incubated with PhIP (mean, 3 adducts/108 nucleotides), N-hydroxy-PhIP (2736/108), or B[a]P (1/108). IQ-DNA adducts were detected in 5/6 tissues (mean, 1/108). The CYP1 inhibitor a-naphthoflavone (10mM) reduced B[a]P-DNA adduct formation in tissues from two individuals by 96% and 64%, respectively. This pilot study shows that human prostate tissue can metabolically activate ‘cooked meat’ carcinogens, a process that could contribute to prostate cancer development. A Williams, FL Martin, 1GH Muir, A Hewer, PL Grover and DH Phillips Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, SM2 5NG. 1Department of Urologyy, Kings College Hospital, Denmark Hill, Camberwell, SE5 9RS. Copyright (c) 1999-2001 GH Muir. All rights reserved. [email protected]
How to find us email us Work suggesting that some food substances may be linked to prostate cancer formation: current research is examining ways of reversing this and detailing possible pathways. The full paper is published in Carcinogenesis Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue Epidemiological evidence suggests a link between meat consumption and prostate cancer. In this study, benign prostatic hyperplasia tissues, obtained by transurethral resection or radical retropubic prostatectomy from UK-resident individuals (n=18), were examined for CYP1 expression and for their ability, in short term organ culture, to metabolically activate carcinogens found in cooked meat. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of CYP1 expression detected CYP1A2 mRNA transcripts in the prostates of 4/4 individuals, as well as mRNA transcripts from CYP1A1 and CYP1B1. The compounds tested for metabolic activation were 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 500mM, n=9) and its metabolite N-hydroxy PhIP (20mM, n=8), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 500mM, n=6) and benzo[a]pyrene (B[a]P, 50mM, n=5). After incubation (PFMR medium, 22h, 37°C) DNA was isolated from tissue fragments and DNA adducts were detected and quantified by 32P-postlabelling analysis. DNA adduct formation was detected in all samples incubated with PhIP (mean, 3 adducts/108 nucleotides), N-hydroxy-PhIP (2736/108), or B[a]P (1/108). IQ-DNA adducts were detected in 5/6 tissues (mean, 1/108). The CYP1 inhibitor a-naphthoflavone (10mM) reduced B[a]P-DNA adduct formation in tissues from two individuals by 96% and 64%, respectively. This pilot study shows that human prostate tissue can metabolically activate ‘cooked meat’ carcinogens, a process that could contribute to prostate cancer development. A Williams, FL Martin, 1GH Muir, A Hewer, PL Grover and DH Phillips Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, SM2 5NG. 1Department of Urologyy, Kings College Hospital, Denmark Hill, Camberwell, SE5 9RS. Copyright (c) 1999-2001 GH Muir. All rights reserved. [email protected]
Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue
Epidemiological evidence suggests a link between meat consumption and prostate cancer. In this study, benign prostatic hyperplasia tissues, obtained by transurethral resection or radical retropubic prostatectomy from UK-resident individuals (n=18), were examined for CYP1 expression and for their ability, in short term organ culture, to metabolically activate carcinogens found in cooked meat. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of CYP1 expression detected CYP1A2 mRNA transcripts in the prostates of 4/4 individuals, as well as mRNA transcripts from CYP1A1 and CYP1B1. The compounds tested for metabolic activation were 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 500mM, n=9) and its metabolite N-hydroxy PhIP (20mM, n=8), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 500mM, n=6) and benzo[a]pyrene (B[a]P, 50mM, n=5). After incubation (PFMR medium, 22h, 37°C) DNA was isolated from tissue fragments and DNA adducts were detected and quantified by 32P-postlabelling analysis. DNA adduct formation was detected in all samples incubated with PhIP (mean, 3 adducts/108 nucleotides), N-hydroxy-PhIP (2736/108), or B[a]P (1/108). IQ-DNA adducts were detected in 5/6 tissues (mean, 1/108). The CYP1 inhibitor a-naphthoflavone (10mM) reduced B[a]P-DNA adduct formation in tissues from two individuals by 96% and 64%, respectively. This pilot study shows that human prostate tissue can metabolically activate ‘cooked meat’ carcinogens, a process that could contribute to prostate cancer development. A Williams, FL Martin, 1GH Muir, A Hewer, PL Grover and DH Phillips Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, SM2 5NG. 1Department of Urologyy, Kings College Hospital, Denmark Hill, Camberwell, SE5 9RS.
Work suggesting that some food substances may be linked to prostate cancer formation: current research is examining ways of reversing this and detailing possible pathways.
The full paper is published in Carcinogenesis
Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue
Epidemiological evidence suggests a link between meat consumption and prostate cancer. In this study, benign prostatic hyperplasia tissues, obtained by transurethral resection or radical retropubic prostatectomy from UK-resident individuals (n=18), were examined for CYP1 expression and for their ability, in short term organ culture, to metabolically activate carcinogens found in cooked meat. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of CYP1 expression detected CYP1A2 mRNA transcripts in the prostates of 4/4 individuals, as well as mRNA transcripts from CYP1A1 and CYP1B1. The compounds tested for metabolic activation were 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 500mM, n=9) and its metabolite N-hydroxy PhIP (20mM, n=8), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 500mM, n=6) and benzo[a]pyrene (B[a]P, 50mM, n=5). After incubation (PFMR medium, 22h, 37°C) DNA was isolated from tissue fragments and DNA adducts were detected and quantified by 32P-postlabelling analysis. DNA adduct formation was detected in all samples incubated with PhIP (mean, 3 adducts/108 nucleotides), N-hydroxy-PhIP (2736/108), or B[a]P (1/108). IQ-DNA adducts were detected in 5/6 tissues (mean, 1/108). The CYP1 inhibitor a-naphthoflavone (10mM) reduced B[a]P-DNA adduct formation in tissues from two individuals by 96% and 64%, respectively. This pilot study shows that human prostate tissue can metabolically activate ‘cooked meat’ carcinogens, a process that could contribute to prostate cancer development. A Williams, FL Martin, 1GH Muir, A Hewer, PL Grover and DH Phillips Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, SM2 5NG. 1Department of Urologyy, Kings College Hospital, Denmark Hill, Camberwell, SE5 9RS.
Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue
[if !supportEmptyParas] Epidemiological evidence suggests a link between meat consumption and prostate cancer. In this study, benign prostatic hyperplasia tissues, obtained by transurethral resection or radical retropubic prostatectomy from UK-resident individuals (n=18), were examined for CYP1 expression and for their ability, in short term organ culture, to metabolically activate carcinogens found in cooked meat. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of CYP1 expression detected CYP1A2 mRNA transcripts in the prostates of 4/4 individuals, as well as mRNA transcripts from CYP1A1 and CYP1B1. The compounds tested for metabolic activation were 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 500mM, n=9) and its metabolite N-hydroxy PhIP (20mM, n=8), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 500mM, n=6) and benzo[a]pyrene (B[a]P, 50mM, n=5). After incubation (PFMR medium, 22h, 37°C) DNA was isolated from tissue fragments and DNA adducts were detected and quantified by 32P-postlabelling analysis. DNA adduct formation was detected in all samples incubated with PhIP (mean, 3 adducts/108 nucleotides), N-hydroxy-PhIP (2736/108), or B[a]P (1/108). IQ-DNA adducts were detected in 5/6 tissues (mean, 1/108). The CYP1 inhibitor a-naphthoflavone (10mM) reduced B[a]P-DNA adduct formation in tissues from two individuals by 96% and 64%, respectively. This pilot study shows that human prostate tissue can metabolically activate ‘cooked meat’ carcinogens, a process that could contribute to prostate cancer development.
A Williams, FL Martin, 1GH Muir, A Hewer, PL Grover and DH Phillips
Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, SM2 5NG.
1Department of Urologyy, Kings College Hospital, Denmark Hill, Camberwell, SE5 9RS.
Copyright (c) 1999-2001 GH Muir. All rights reserved.
[email protected]