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Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma.
The risk of cancer of the cervix is linked with sexual behaviour. Although infectious agents such as human papillomaviruses (HPVs) are implicated, these alone may be insufficient to induce the disease. We have investigated the potential role of oxidation products of the polyamines spermine and sperm...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1995
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033920/ https://www.ncbi.nlm.nih.gov/pubmed/7577467 |
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author | Fernandez, C. Sharrard, R. M. Talbot, M. Reed, B. D. Monks, N. |
author_facet | Fernandez, C. Sharrard, R. M. Talbot, M. Reed, B. D. Monks, N. |
author_sort | Fernandez, C. |
collection | PubMed |
description | The risk of cancer of the cervix is linked with sexual behaviour. Although infectious agents such as human papillomaviruses (HPVs) are implicated, these alone may be insufficient to induce the disease. We have investigated the potential role of oxidation products of the polyamines spermine and spermidine and the diamine putrescine in seminal plasma (SP) as co-factors in the development of cervical cancer. These amines are oxidised by polyamine oxidase (PAO) and diamine oxidase (DAO) to generate oxygen radicals and hydrogen peroxide, reactive aldehydes and acrolein, which are likely to exert local mutagenic, cytotoxic and immunosuppressive effects in vivo. Using a chemiluminescence assay, we determined the levels of these amines in 187 samples of SP. Spermine plus spermidine, as substrates for PAO, were present in a range equivalent to 0-4.8 mg ml-1 spermine. Putrescine, as a substrate for DAO, was detectable in only 4 of 40 samples assayed (range 0-168 micrograms ml-1) and constitutes a minor component of the oxidisable content of SP. Cervical mucus (126 samples) was assayed for the presence of PAO and DAO. Both enzymes were present in 14.3% of the samples, PAO only in 21.4%, DAO only in 15.1% and neither enzyme in 49.2%. PAO levels ranged from 0 to 0.828 pmol peroxide generated min-1 mg-1 mucus and DAO levels ranged from 0 to 7.0 pmol peroxide generated min-1 mg-1 mucus. These results suggest that sexual activity in the absence of physical barrier contraception may lead to the generation of mutagenic and immunosuppressive polyamine oxidation products within the female genital tract. We thus propose that women with high levels of PAO and/or DAO in their cervical mucus may be at increased risk of cervical cancer, especially if the male partner's SP shows high polyamine levels. HPV infection may synergise with the effects of polyamine oxidation by suppressing apoptosis in keratinocytes carrying potentially oncogenic mutations, leading to the survival and proliferation of transformed cells in the cervix. |
format | Text |
id | pubmed-2033920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1995 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20339202009-09-10 Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma. Fernandez, C. Sharrard, R. M. Talbot, M. Reed, B. D. Monks, N. Br J Cancer Research Article The risk of cancer of the cervix is linked with sexual behaviour. Although infectious agents such as human papillomaviruses (HPVs) are implicated, these alone may be insufficient to induce the disease. We have investigated the potential role of oxidation products of the polyamines spermine and spermidine and the diamine putrescine in seminal plasma (SP) as co-factors in the development of cervical cancer. These amines are oxidised by polyamine oxidase (PAO) and diamine oxidase (DAO) to generate oxygen radicals and hydrogen peroxide, reactive aldehydes and acrolein, which are likely to exert local mutagenic, cytotoxic and immunosuppressive effects in vivo. Using a chemiluminescence assay, we determined the levels of these amines in 187 samples of SP. Spermine plus spermidine, as substrates for PAO, were present in a range equivalent to 0-4.8 mg ml-1 spermine. Putrescine, as a substrate for DAO, was detectable in only 4 of 40 samples assayed (range 0-168 micrograms ml-1) and constitutes a minor component of the oxidisable content of SP. Cervical mucus (126 samples) was assayed for the presence of PAO and DAO. Both enzymes were present in 14.3% of the samples, PAO only in 21.4%, DAO only in 15.1% and neither enzyme in 49.2%. PAO levels ranged from 0 to 0.828 pmol peroxide generated min-1 mg-1 mucus and DAO levels ranged from 0 to 7.0 pmol peroxide generated min-1 mg-1 mucus. These results suggest that sexual activity in the absence of physical barrier contraception may lead to the generation of mutagenic and immunosuppressive polyamine oxidation products within the female genital tract. We thus propose that women with high levels of PAO and/or DAO in their cervical mucus may be at increased risk of cervical cancer, especially if the male partner's SP shows high polyamine levels. HPV infection may synergise with the effects of polyamine oxidation by suppressing apoptosis in keratinocytes carrying potentially oncogenic mutations, leading to the survival and proliferation of transformed cells in the cervix. Nature Publishing Group 1995-11 /pmc/articles/PMC2033920/ /pubmed/7577467 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Fernandez, C. Sharrard, R. M. Talbot, M. Reed, B. D. Monks, N. Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma. |
title | Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma. |
title_full | Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma. |
title_fullStr | Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma. |
title_full_unstemmed | Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma. |
title_short | Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma. |
title_sort | evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033920/ https://www.ncbi.nlm.nih.gov/pubmed/7577467 |
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