Since many risk factors are associated with the development of uterine adenocarcinomas in humans, the etiology is unclear in most cases, although it has been pointed out that estrogen may play essential roles. To clarify the effects of exposure to p-tert-octylphenol (OP), an environmental xenoestrogen, on uterine carcinogenesis, adult Donryu rats were initiated with a single intrauterine treatment of N-ethyl-N′ ′ ′ ′-nitro-N-nitrosoguanidine (ENNG) at 11 weeks of age and exposed thereafter to 100 mg/kg OP by s.c. injection until 15 months of age. Adult ovariectomized (OVX) rats were also treated in a similar way. OP had no effect on occurrence of persistent estrus in middle age, although uterotrophic effects were obvious in OVX rats. At the termination, development of uterine adenocarcinomas was significantly increased in animals exposed to OP during adulthood. No tumors, but a few focal hyperplasias, developed in OVX rats. These findings suggest that OP has tumor-promoting effects on ENNG-treated endometrium of rats, possibly due to direct action on the uterus, as indicated by the uterotrophic effect when a high dose of OP was given. The results provide clues to the mechanisms of influence of hormonal disrupters on uterine carcinogenesis.
Key words: Octylphenol -Rat -Uterine adenocarcinoma -AdulthoodRecently, the possible adverse consequences arising from the release of man-made substances with estrogenic, anti-estrogenic or androgenic properties, so-called endocrine disrupting chemicals (EDCs), into the environment have become an important social issue. p-tert-Octylphenol [OP;1,3,phenol, Fig. 1], one of the alkylphenols (APs), is listed as an EDC with estrogenic activity in vitro 1,2) and in vivo. 3,4) Environmental OP is thought to be derived from biodegradation of non-ionic surfactants, alkylphenol polyethoxylates (APEOs), 5) and is found in the sludge of sewage-treatment plants as well as in the river and sea sediments.1, 6) It has been pointed out that human exposure to OP may occur not only through drinking water extracted from polluted rivers and foods from fields contaminated with sewage sludge, but also by contact with manufactured and/or breakdown products, such as absorption through skin from shampoos and cosmetics, or inhalation and ingestion from pesticide sprays.
7)While APs, including OP, exist at only very low concentrations in the environment (below 1 µg/liter in water in Europe) 8) and are markedly less estrogenic than estradiol-17β (E2), this does not rule out potential toxicity of chronic exposure to animals and human beings, taking into account the evidence of bioaccumulation in fish.
9)Carcinogenicity is the most important possible adverse consequence of chemicals including EDCs. In fact, it has been hypothesized that environmental estrogens, including APs, may be causative agents for breast cancer in humans.10) The uterine adenocarcinoma is one of the most common malignant tumors in women.11) While its etiology remains largely unclear, it has been pointed out that hormones such as estroge...