Fernandez C, Sharrard R M, Talbot M, Reed B D, Monks N
Institute for Cancer Studies, University of Sheffield Medical School, UK.
Br J Cancer. 1995 Nov;72(5):1194-9. doi: 10.1038/bjc.1995.485.
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.
宫颈癌风险与性行为有关。虽然人乳头瘤病毒（HPV）等感染因子与之相关，但仅这些因素可能不足以引发该病。我们研究了精胺、亚精胺的氧化产物以及二胺腐胺在精浆（SP）中作为宫颈癌发展辅助因子的潜在作用。这些胺类被多胺氧化酶（PAO）和二胺氧化酶（DAO）氧化，生成氧自由基和过氧化氢、反应性醛类及丙烯醛，它们可能在体内发挥局部诱变、细胞毒性和免疫抑制作用。通过化学发光分析，我们测定了187份精浆样本中这些胺类的水平。作为PAO底物的精胺加亚精胺的含量范围相当于0至4.8毫克/毫升精胺。作为DAO底物的腐胺，在所检测的40份样本中仅在4份中可检测到（范围为0至168微克/毫升），且是精浆可氧化成分中的次要组分。对126份宫颈黏液样本检测了PAO和DAO的存在情况。两种酶均存在于14.3%的样本中，仅PAO存在于21.4%的样本中，仅DAO存在于15.1%的样本中，两种酶均不存在于49.2%的样本中。PAO水平范围为0至0.828皮摩尔过氧化氢生成量/分钟·毫克-1黏液，DAO水平范围为0至7.0皮摩尔过氧化氢生成量/分钟·毫克-1黏液。这些结果表明，在无物理屏障避孕措施的情况下进行性行为可能导致女性生殖道内产生诱变和免疫抑制性多胺氧化产物。因此我们提出，宫颈黏液中PAO和/或DAO水平高的女性患宫颈癌的风险可能增加，尤其是如果男性伴侣的精浆显示多胺水平高。HPV感染可能通过抑制携带潜在致癌突变的角质形成细胞中的细胞凋亡，与多胺氧化的作用协同，导致宫颈中转化细胞的存活和增殖。
