Abstract
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.
Highlights
0.828 pmol peroxide generated min-' mg'I mucus and diamine oxidase (DAO) levels ranged from 0 to 7.0 pmol peroxide generated min-' mg-' mucus
0.828 pmol peroxide generated min-' mg'I mucus and DAO levels ranged from 0 to 7.0 pmol peroxide generated min-' mg-' mucus. These results suggest that sexual activity in the absence of physical bamrer contraception may lead to the generation of mutagenic and immunosuppressive polyamine oxidation products within the female genital tract
We propose that women with high levels of polyamine oxidase (PAO) and/or DAO in their cervical mucus may be at increased risk of cervical cancer, especially if the male partner's Seminal plasma (SP) shows high polyamine levels
Summary
Polyamine (spermine and spermidine) levels were determined using the chemiluminescence assay described by Fenandez et a al. (1994) as follows: SP samples were diluted 1:60 in reaction buffer (1 mM glycine hydrogen chloride pH 7.4/0.01 mM sodium carbonate). Polyamine (spermine and spermidine) levels were determined using the chemiluminescence assay described by Fenandez et a al. (1994) as follows: SP samples were diluted 1:60 in reaction buffer (1 mM glycine hydrogen chloride pH 7.4/0.01 mM sodium carbonate). An aliquot of 20 id of diluted SP was mixed with 1 ml of reaction buffer in a stoppered cuvette, E. 10 j of purified PAO was added, and the cuvette was incubated at room temperature for 1 h. C microperoxidase (final concentration 10 jag ml '). Light emitted was measured using a BioOrbit 1251 luminometer with BioOrbit 1257 software ('Phagocytosis' programme) or a a. BioOrbit 1250 luminometer linked to a standard chart a recorder. Putrescine was assayed by substituting DAO for PAO to a final concentration of lSMgml-I and incubating at 3rC for 24h. Detection ofpolyanine and diamine oxidases in cervical mucus pllmsa uSm e pb N(187)odNcoernvnixb
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
