Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma

Smm_ary 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- ' spermine. Putrescine, as a substrate for DAO, was detectable in only 4 of 40 samples assayed (range 0-168 pg ml-') 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- ' 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 product