TEDX The Endocrine Disruption Exchange 211 Grand Ave, Ste. 114, P.O. Box 1407, Paonia, CO 81428 970-527-4082 [email protected] References Acevedo HF, Tong JY, Hartsock RJ. 1995 . Human chorionic gonadotropin-beta subunit gene expression in cultured human fetal and cancer cells of different types and origins. Cancer 76:1467-1475. Abstract: BACKGROUND. The authors' previous investigations using living cultured human cancer cells and cells isolated from cancer tissues, analytical flow cytometry, and monoclonal antibodies directed to epitopes located in five different sites of the human chorionic gonadotropin (hCG) molecule, identified the presence of membrane-associated hCG, its subunits and fragments, by cells from all cancers, irrespective of type and origin, indicating that the expression of these sialoglycoproteins is a common phenotypic characteristic of cancer. Although benign neoplasms do not express these compounds, cultured human embryonic and fetal cells also express the same materials. To corroborate these findings, five fetal cell lines and 28 cancer cell lines were randomly selected from those previously studied, to determine the presence of translatable levels of hCG-beta (hCG beta) mRNA. METHODS. All cell lines were grown under identical conditions. Determination of hCG beta mRNA was made by extracting the total RNA from the cells, followed by synthesis of cDNA with RNase H- reverse transcriptase and polymerase chain reaction amplification using specific hCG beta-luteinizing hormone-beta (hLH beta) primers. The presence of amplified hCG beta cDNA was corroborated by hybridization of the product with an hCG beta-specific oligonucleotide and Southern blot analyses of the hybridization products. Gestational choriocarcinoma cells and HeLa adenocarcinoma of cervical cells, known producers of biologically active hCG, were positive control subjects, and human pituitary cells were used as negative control subjects. RESULTS. The results showed single and multiple hCG beta gene activation by the fetal cells and the different types of cancer, indicating that at any given time, there is the possibility of activation of as many as four genes of the six genes of the hCG beta-hLH beta gene cluster, even though alternative gene splicing cannot be ruled out. CONCLUSIONS. In addition to the authors' previous findings, the results of these studies support the concept that cancer is a problem of development and differentiation, and, to the authors' knowledge, prove definitively for the first time that synthesis and expression of hCG, its subunits, and its fragments, is a common biochemical denominator of cancer, providing the scientific basis for studies of its prevention and/or control by active and/or passive immunization against these sialoglycoproteins. Acharya S, Jayabose S, Kogan SJ, Tugal O, Beneck D, Leslie D, Slim M. 1997. Prenatally diagnosed neuroblastoma. Cancer 80:304-310. Abstract: BACKGROUND: Prenatally diagnosed neuroblastomas have been reported in increasing numbers over the past several years, and there are now a few reviews based on up to 21 cases. The purpose of this article is to review the clinical and biologic features of prenatally diagnosed neuroblastoma based on a review of 55 cases. METHODS: A review was conducted of 3 cases seen at the study institution and 52 other cases reported thus far in the literature. RESULTS: Prenatal diagnosis was made usually after 32 weeks of gestation. Approximately 93% of the tumors were adrenal in origin, and 44% of these were cystic. Thirty-seven patients (67%) had Stage I disease, 12 (22%) had Stage IV-S disease, and only 3 (5%) had Stage IV disease. The DNA index was favorable (> 1) in 14 of 16 patients studied. None of these 16 patients studied had amplification of the N-myc oncogene. Catecholamines were elevated in only 33% of the patients. The liver was the most common site of dissemination, which was observed in 25% of patients; bone involvement was not observed in any patient. Ultrasonography failed to detect existing hepatic metastasis in three patients. Primary surgical resection was performed in 47 patients (85%). Chemotherapy was given to five patients and radiotherapy to three. Of the 50 patients for whom follow-up information was available, 45 (90%) were alive at a range of 2-120 months from diagnosis. CONCLUSIONS: Prenatally diagnosed neuroblastomas are predominantly adrenal in origin and frequently cystic. The liver is the most common site of dissemination and bone involvement is notably absent. The vast majority of these infants have a favorable stage of disease (I, II, and IV-S) and favorable biologic features, and consequently have an excellent prognosis. Although surgery alone is curative for most patients, a period of observation may avoid surgery in some individuals who may achieve spontaneous regression. Adami HO, Persson I, Ekbom A, Wolk A, Ponten J, Trichopoulos D. 1995. The aetiology and pathogenesis of human breast cancer. Mutation Research-Fundamental & Molecular Mechanisms of Mutagenesis 333:29- 35. Abstract: Whilst investigators have clearly shown that non-hereditary factors dominate the aetiology of human breast cancer, they have failed to identify quantitatively important causes, and prospects for prevention remain indeed limited. However, progress in epidemiological and basic research has taken place during the last few years. Current evidence suggests that breast cancer may be affected by the intra-uterine environment, that exposures during adolescence are particularly important, and that pregnancy has a dual effect on breast cancer risk: an early increase followed by long-term protection. Great variation exists in the structural development of the breast ductal system already in the newborn - and by inference in utero - and a pregnancy induces permanent structural changes in the mammary gland. We suggest that these observations fit into an aetiological model with the following key components: (1) breast cancer risk depends on the number of cells at risk, the susceptibility of individual cells to malignant transformation, and on the degree of cellular proliferation, notably cells which can act as founders of breast cancer; (2) the number of target cells is determined by the hormonal environment mainly early in life, perhaps already in utero; (3) in adult life, hormones which are non-genotoxic, increase breast cancer risk by increasing selective cell proliferation and thus number of target cells and the risk of retention of spontaneous somatic mutations; (4) while a pregnancy stimulates the growth of already malignant cells or cells close to malignant transformation (and thereby entails a short-term risk increase) the dominating long-term protection occurs due to permanent structural changes, terminal differentiation and perhaps decreased cell proliferation and carcinogen-binding in combination. Adami J, Glimelius B, Cnattingius S, Ekbom A, Zahm SH, Linet M, Zack M. 1996. Maternal and perinatal factors associated with non-Hodgkin's lymphoma among children. Int J Cancer 65:774-777. Abstract: This nested case-control study based on 1.7 million live births in Sweden explores the associations between maternal and perinatal factors and the occurrence of childhood non-Hodgkin's lymphoma (NHL). The National Swedish Cancer Registry ascertained 168 cases in successive birth cohorts from 1973 through 1989 recorded in the Swedish Medical Birth Registry. From the nationwide Birth Registry, 5 controls without NHL and alive at the date the case was diagnosed were randomly selected from the pool of children, with each case matched by gender, birth year and birth month. Standardized information on selected maternal and perinatal factors up to one month after delivery were recorded in the Medical Birth Registry. Mothers of children with NHL were more likely than mothers of controls to have undergone Cesarean section [Odds ratio (OR) 1.6] and to have been exposed to paracervical anesthesia during delivery (OR 1.8). Children with NHL were more likely than controls to have endocrine-metabolic disorders (OR 3.3). This study is one of the largest focusing on the etiology of childhood NHL. Most of the maternal and perinatal characteristics studied did not markedly affect risk for childhood NHL, which may be due to maternal and perinatal factors not included in these data or to exposures later in life. (C) 1996 Wiley-Liss, Inc. Adey WR, Byus CV, Cain CD, Higgins RJ, Jones RA, Kean CJ, Kuster N, MacMurray A, Stagg RB, Zimmerman G, Phillips JL, Haggren W. 1999. Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves. Radiat Res 152: 293-302. Abstract: We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosourea (ENU) in utero, followed by intermittent digital- phone field exposure for 24 months. Far-field exposures began on gestational day 19 and continued until weaning at age 21 days. Near-field exposures began at 35 days and continued for the next 22 months, 4 consecutive days weekly, 2 h/day. SAR levels simulated localized peak brain exposures of a cell phone user. Of the 236 original rats, 182 (77%) survived to the termination of the whole experiment and were sacrificed at age 709-712 days. The 54 rats (23%) that died during the study ("preterm rats") formed a separate group for some statistical analyses. There was no evidence of tumorigenic effects in the CNS from exposure to the TDMA field. However, some evidence of tumor-inhibiting effects of TDMA exposure was apparent. Overall, the TDMA field-exposed animals exhibited trends toward a reduced incidence of spontaneous CNS tumors (P < 0. 16, two-tailed) and ENU-induced CNS tumors (P < 0.16, two-tailed). In preterm rats, where primary neural tumors were determined to be the cause of death, fields decreased the incidence of ENU-induced tumors (P < 0.03, two-tailed).