EVALUATION OF THE SIGNIFICANCE OF POLYAMINES AND THEIR OXIDASES IN THE ETIOLOGY OF HUMAN CERVICAL-CARCINOMA

The risk of cancer of the cenix is linked with sexual behaviour. Altho ugh infectious agents such as human papillomaviruses (HPVs) are implic ated, these alone may be insufficient to induce the disease. We have i nvestigated 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 im munosuppressive effects in vivo. Using a chemiluminescence assay, we d etermined the levels of these amines in 187 samples of SP. Spermine pl us spermidine, as substrates for PAO, were present in a range equivale nt to 0-4.8 mg ml(-1) spermine. Putrescine, as a substrate for DAO, wa s detectable in only 4 of 40 samples assayed (range 0-168 mu g ml(-1)) and constitutes a minor component of the oxidisable content of SP. Ce rvical 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 fro m 0 to 0.828 pmol peroxide generated min(-1) mg(-1) mucus and DAO leve ls 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 immu nosuppressive polyamine oxidation products within the female genital t ract. 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, esp ecially if the male partner's SP shows high polyamine levels. HPV infe ction may synergise with the effects of polyamine oxidation by suppres sing apoptosis in keratinocytes carrying potentially oncogenic mutatio ns, leading to the survival and proliferation of transformed cells in the cervix.