Murrell T G
Department of Community Medicine, University of Adelaide, South Australia.
Med Hypotheses. 1991 Dec;36(4):389-96. doi: 10.1016/0306-9877(91)90018-t.
Damage to the breast epithelium by chemical carcinogens as products of oxygen free radical release can lead to fibroblast proliferation, hyperplasia of epithelium, cellular atypia and breast cancer. Chemical carcinogens may accumulate in breast fluid in the non-lactating breast consequent to superoxide free radical production which occurs via the adenosine triphosphate (ATP) hypoxanthine pathway. This pathway is initiated by hypoxia of local tissue. Under hypoxic conditions ATP is broken down to form hypoxanthine. Hypoxanthine itself is broken down to produce xanthine and then uric acid. This results in the production of superoxide free radicals, the products of which are carcinogenic. The development of localized hypoxia, which is central to this hypothesis, is caused by acinal gland distention from fluid secreted by raised prolactin levels in the absence of oxytocin. Stimulation of the nipple in a non-lactating breast may raise plasma oxytocin and lower plasma prolactin levels. Contraction of the myoepithelial cells of the breast under the influence of oxytocin would relieve distention of the acinal glands and thus reduce hypoxia and the generation of lipid peroxidoses as products of free radical damage. The epidemiology of breast fibrosis and cancer support the notion that lack of nipple stimulation over time may be a significant variable. A review of this literature linked with current biochemical work on fibrosis and carcinogenesis suggest that draining the breasts of the products of superoxide free-radical release by the encouragement of regular nipple erections may prevent such breast disease.
作为氧自由基释放产物的化学致癌物对乳腺上皮造成的损伤，可导致成纤维细胞增殖、上皮增生、细胞异型性及乳腺癌。化学致癌物可能会因通过三磷酸腺苷（ATP）次黄嘌呤途径产生超氧自由基而在非哺乳期乳腺的乳腺液中蓄积。该途径由局部组织缺氧引发。在缺氧条件下，ATP分解形成次黄嘌呤。次黄嘌呤本身再分解产生黄嘌呤，进而生成尿酸。这会导致超氧自由基的产生，其产物具有致癌性。局部缺氧的发生是这一假说的核心，它是由在缺乏催产素的情况下催乳素水平升高所分泌的液体导致腺泡扩张引起的。刺激非哺乳期乳腺的乳头可能会提高血浆催产素水平并降低血浆催乳素水平。在催产素的影响下，乳腺肌上皮细胞的收缩会缓解腺泡的扩张，从而减少缺氧以及作为自由基损伤产物的脂质过氧化物的产生。乳腺纤维化和癌症的流行病学支持这样一种观点，即长期缺乏乳头刺激可能是一个重要变量。对该文献的回顾以及当前关于纤维化和致癌作用的生化研究表明，通过促使乳头定期勃起排出超氧自由基释放的产物，可能预防此类乳腺疾病。
