Development Of Childhood Leukemia Research Articles

Role of Maternal Diet in the Risk of Childhood Acute Leukemia: A Systematic Review and Meta-Analysis.

Many studies have investigated the etiology of acute leukemia, one of the most common types of cancer in children; however, there is a lack of clarity regarding preventable risk factors. This systematic review and meta-analysis aimed to summarize the current evidence regarding the role of maternal dietary factors in the development of childhood leukemia. All epidemiological studies published until July 2022 that evaluated maternal dietary risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science) without limits of publication year or language. A total of 38 studies (1 prospective cohort study, 34 case-control studies and 3 studies with pooled analysis) were included. The published risk estimates were combined into a meta-analysis, using the Generic Inverse Variance method. The maternal consumption of fruits (two or more daily servings vs. less) was inversely associated with acute lymphoblastic leukemia (odds ratio = 0.71; 95% CI, 0.59-0.86), whereas maternal coffee intake (higher than two cups per day vs. no consumption) was associated with an increased risk of acute lymphoblastic leukemia (odds ratio = 1.45; 95% CI, 1.12-1.89). Despite these findings, more high-quality research from cohort studies and the identification of causal factors are needed to develop evidence-based and cost-effective prevention strategies applicable at the population level. Review Registration: PROSPERO registration no. CRD42019128937.

P06-18 Influence of extremely low frequency magnetic fields on the development of childhood leukemia – an experimental study in a susceptible mouse model

P06-18 Influence of extremely low frequency magnetic fields on the development of childhood leukemia – an experimental study in a susceptible mouse model

Residential proximity to plant nurseries and risk of childhood leukemia

BackgroundPesticides are a potential risk factor for childhood leukemia. Studies evaluating the role of prenatal and/or early life exposure to pesticides in the development of childhood leukemia have produced a range of results. In addition to indoor use of pesticides, higher risks have been reported for children born near agricultural crops. No studies have looked at pesticide exposure based on proximity of birth residence to commercial plant nurseries, even though nurseries are located much closer to residences than agricultural crops and can potentially result in chronic year-round pesticide exposure. ObjectivesTo evaluate whether risk of childhood leukemia is associated with pesticide use as determined by distance of residence at birth to commercial, outdoor plant nurseries. MethodsWe conducted a large statewide, record-based case-control study of childhood leukemia in California, which included 5788 childhood leukemia cases and an equal number of controls. Pesticide exposure was based on a spatial proximity model, which combined geographic information system data with aerial satellite imagery. ResultsOverall, the results supported an increased childhood leukemia risk only for birth residences very close to nurseries. For birth residences less than 75 m from plant nurseries, we found an increased risk of childhood leukemia (odds ratio (OR) 2.40, 95% confidence interval (CI) 0.99-5.82) that was stronger for acute lymphocytic leukemia (OR 3.09, 95% CI 1.14-8.34). DiscussionThe association was robust to choices of reference group, cut points and data quality. Our findings suggest that close proximity to plant nurseries may be a risk factor for childhood leukemia and that this relationship should be further evaluated.

Induction of AML Preleukemic Fusion Genes in HSPCs and DNA Damage Response in Preleukemic Fusion Gene Positive Samples.

Preleukemic fusion genes (PFGs) occurring after DNA damage in hematopoietic stem progenitor cells (HSPCs) in utero often represent the initial event in the development of childhood leukemia. While the incidence of PFGs characteristic for acute lymphoblastic leukemia (ALL) was relatively well examined by several research groups and estimated to be 1–5% in umbilical cord blood (UCB) of healthy newborns, PFGs that are relevant to acute myeloid leukemia (AML) were poorly investigated. Therefore, this study is focused on the estimation of the incidence of the most frequent AML PFGs in newborns. For the first time, this study considered the inducibility of AML PFGs in different subsets of UCB HSPCs by low-dose γ-rays and also compared endogenous DNA damage, apoptosis, and reactive oxygen species (ROS) level between UCB samples containing or lacking AML PFGs. We found that: (i) the incidence of AML PFGs in UCB was 3.19% for RUNX1-RUNX1T1, 3.19% for PML-RARα, and 1.17% for KMT2A-MLLT3, (ii) 50 cGy of γ-rays did not induce RUNX1-RUNX1T1, PML-RARα, or KMT2A-MLLT3 PFGs in different subsets of sorted and expanded HSPCs, and (iii) the AML PFG+ samples accumulated the same level of endogenous DNA damage, as measured by the γH2AX/53BP1 focus formation, and also the same ROS level, and apoptosis as compared to PFG− controls. Our study provides critical insights into the prevalence of AML PFGs in UCB of newborns, without the evidence of a specific HSPC population more susceptible for PFG formation after irradiation to low-dose γ-rays or increased amount of ROS, apoptosis and DNA damage.

The association between maternal folic acid supplementation and risk of childhood leukeamia: a systematic review focusing on the potential role of epigenetic mechanisms

Rationale: Folate is considered a key nutrient especially during embryogenesis. Consumption of folate doses during periconceptional period and pregnancy, has been linked to modifications of the epigenetic mechanisms and gene expression in the fetus. It has been hypothesized that insufficient intake of maternal folate could result in impairment of methylgroup supply, altered DNA methylation and carcinogenesis both in utero and in early life. This systematic review aimed to explore the effect of maternal folic acid supplementation on the development of childhood leukaemia, the most common type of peadiatric cancer.

Evaluation of diet as a risk factor in the development of childhood leukaemia: a case control study.

To evaluate probable association of dietary risk factors with childhood leukaemia. The case-control study was conducted at the Children Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from January to December 2017, and comprised children of either gender aged 2-12 years with recently diagnosed acute lymphocytic or acute myelocytic leukaemia An age and gender matched equal group of healthy children was taken as controls. Dietary-intake data was collected for six food groups, namely raw vegetables, fresh fruits, packed fruit juices, caffeinated drinks, junk foods, and processed/precooked food items. Frequency of the selected food group consumption was summarised in six categories: rarely/never, 1-3 days/week, 4-6 days/week, once daily, twice daily and thrice daily. Data was collected through interviews with the mothers using a pre-designed questionnaire, and was analysed using SPSS 21. Of the 90 subjects, 45(50%) were in each of the two groups. There were no differences in baseline characteristics between the two groups (p>0.05). Consumption of caffeinated drinks and junk food was significantly higher in cases (p=0.001) while controls showed significantly higher consumption of fresh fruits (p=0.0012). No significant difference was noted for consumption of vegetables, packed fruit juices and processed food between the groups (p> 0. 05 ). Higher consumption of caffeinated drinks and junk food was observed in cases compared to controls.

Investigating Benzene and Metabolite Mediated Alterations in Nrf2 Signaling in Murine Fetal Liver Cells

Leukemia is a cancer of the blood, where the body produces an overabundance of immature white blood cells. It is the most common childhood cancer and possibly originates from chemical exposure during fetal development. Understanding the molecular mechanism and causes of childhood leukemia will help the development of therapeutic and preventative strategies to reduce and treat occurrences of this cancer. Benzene is a non-polar aromatic ring that has been confirmed to cause leukemia in adults. Benzene metabolites can generate free radicals that could potentially be involved in the development of childhood leukemia through in utero exposures. It is found in tobacco smoke, gasoline, industrial solvents and many other substances. Pregnant mothers can be chronically exposed to these substances through daily activities. In order to help determine the mechanism of benzene toxicity, a study was performed to determine the presence of free radicals in the livers of fetal mice at gestation day 14. Fetal liver cell cultures were exposed to varying concentrations of benzene and additional cell cultures were exposed to various concentrations of a benzene metabolite mixture, composed of hydroquinone and benzoquinone. RNA was extracted from these cells and converted into complementary DNA. cDNA was then used in quantitative polymerase chain reactions to analyze a set of genes that are regulated by an antioxidant pathway. This pathway can be activated in response to oxidative stress, and a change in gene expression would indicate the presence of benzene or benzene metabolite toxicity in the liver at gestation day 14.

Spatial clustering of childhood leukaemia with the integration of the Paediatric Environmental History

BackgroundLeukaemia remains the most common type of paediatric cancer and its aetiology remains unknown, but considered to be multifactorial. It is suggested that the initiation in utero by relevant exposures and/or inherited genetic variants and, other promotional postnatal exposures are probably required to develop leukaemia. This study aimed to map the incidence and analyse possible clusters in the geographical distribution of childhood acute leukaemia during the critical periods and to evaluate the factors that may be involved in the aetiology by conducting community and individual risk assessments. Materials and methodsWe analysed all incident cases of acute childhood leukaemia (<15 years) diagnosed in a Spanish region during the period 1998–2013. At diagnosis, the addresses during pregnancy, early childhood and diagnosis were collected and codified to analyse the spatial distribution of acute leukaemia. Scan statistical test methodology was used for the identification of high-incidence spatial clusters. Once identified, individual and community risk assessments were conducted using the Paediatric Environmental History. ResultsA total of 158 cases of acute leukaemia were analysed. The crude rate for the period was 42.7 cases per million children. Among subtypes, acute lymphoblastic leukaemia had the highest incidence (31.9 per million children). A spatial cluster of acute lymphoblastic leukaemia was detected using the pregnancy address (p<0.05). The most common environmental risk factors related with the aetiology of acute lymphoblastic leukaemia, identified by the Paediatric Environmental History were: prenatal exposure to tobacco (75%) and alcohol (50%); residential and community exposure to pesticides (62.5%); prenatal or neonatal ionizing radiation (42.8%); and parental workplace exposure (37.5%) ConclusionsOur study suggests that environmental exposures in utero may be important in the development of childhood leukaemia. Due to the presence of high-incidence clusters using pregnancy address, it is necessary to introduce this address into the childhood cancer registers. The Paediatric Environmental History which includes pregnancy address and a careful and comprehensive evaluation of the environmental exposures will allow us to build the knowledge of the causes of childhood leukaemia.

Epidemiology, Risk Assessment of Environmental Carcinogens and Polymorphism in Childhood Leukemia and Solid Tumors: A Study from Gwangju-Chonnam Area, Korea

Purpose: The survival of childhood leukemia and cancer has improved dramatically in developing countries in the last decades. This study represents the outcome of childhood leukemia and solid tumors from a province of Korea with a population of 3.5 million. Although a variety of environmental factors has been implicated in the pathogenesis of carcinogenesis, little is universally accepted for the development of childhood malignancies. Moreover, genetic polymorphisms are known to influence the risk of developing cancers. Thus, this study is aimed to identify environmental factors and genomic variations in the development of childhood leukemia and cancer.Materials and Methods: From 2006 to 2013, a total of 427 children were diagnosed to have childhood leukemia and solid tumors from Gwangju-Chonnam area. The survival was evaluated in these population. For environmental hazard identification, a database of 975 items was collected including a questionnaire of parental environmental and occupational exposure, and mother-child life-style. A total of 335 patients and 378 healthy controls were enrolled in the study. Environmental exposure was assessed by toxicological measurement of house-hold air and water samples. Blood and urine samples were collected for internal dose assessment from patients and controls and their respective parents. Single nucleotide polymorphisms (SNP) were also evaluated for enzymes involved in metabolism, cell cycle regulation, differentiation, and signal transduction.Results: The 5-yr Kaplan-Meier estimated overall survival (OS) for all 427 patients was 80.7±2.2%. The 5-yr OS for 212 leukemia patients was 74.8±3.5%, while that for 215 children with solid tumors was 86.0±2.8%. From the questionnaire, maternal smoking history was the most significant factor associated with leukemia in children [Odds ratio (OR), 4.76 (95% CI, 1.23-18.46)]. Paternal smoking history was also significant [OR, 1.69 (1.04-2.72)]. Carcinogenic exposures in house-hold air and water were not significantly different from controls. For internal dose evaluation, urinary 1-hydroxypyrene concentration was higher in patients (P<0.001), and blood cadmium concentration tended to be higher in patients and their parents. SNP analysis showed that genomic variations of ARID5B and CDKN2A, but not IKZF1, might play an important role in the risk of childhood acute lymphoblastic leukemia in Korea.Conclusion: These results show significant improvement of survival of childhood leukemia and solid tumors in Korea, which is comparable to Western countries. Considering the heterogeneity of childhood cancers and complex pathogenesis of each disease category, a large number of patients are required to elucidate precise association with environmental carcinogens. However, parental smoking is associated with the risk of leukemia. Moreover, ethnic difference in genotypic polymorphism and the susceptibility to malignancies should be contemplated. DisclosuresNo relevant conflicts of interest to declare.

Health effects of extremely low‐frequency magnetic fields: reconsidering the melatonin hypothesis in the light of current data on magnetoreception

The so-called 'Melatonin Hypothesis' proposed that decreased nocturnal production of melatonin (MLT) might explain the increased risk of breast cancer that has been formerly attributed to extremely low-frequency (ELF) magnetic fields (MF) of weak intensity. Although the risk of ELF MF upon breast cancer was later dismissed, repeated reports were published of partial inhibition of MLT secretion in rats under long-term (≥ 4 weeks) exposure to weak ELF MF. Since 2004, however, this topic has not been experimentally studied any more. In the present study, we propose to go back to the MLT hypothesis and apply it to childhood leukemia, for which an increased risk has been robustly associated with residential exposure to ELF MF. Contrary to the original hypothesis, however, we do not consider decreased MLT levels, but disruption of circadian rhythmicity per se as the effector mechanism. Indeed, the role of the circadian timing system in the development of childhood leukemia has been well established. Motivation for going back to the MLT hypothesis comes from recent data that suggest magnetosensory disruption by ELF MF in mammals, and magnetosensitivity in humans, together with current evidence for an influence on circadian rhythmicity from disruption of non-photic sensory stimuli of various natures. We thus suggest further study on circadian rhythmicity in humans (children if possible) under long-term exposure to weak ELF MF.

Maternal smoking during pregnancy and risk for childhood leukemia: A nationwide case–control study in Greece and meta‐analysis

Maternal smoking during pregnancy has been often implicated in the development of childhood leukemia with ambiguous results. Hence, we conducted a meta-analysis aiming to summarize current evidence and quantify any tentative impact. We retrieved one cohort (553 leukemias compared to 1,440,542 children), 20 case-control studies and also analyzed the updated Greek case-control dataset with unpublished data, yielding in total 11,092 cases and 25,221 controls. Odds ratios reported in the studies included ranged from 0.70 to 2.20 for acute lymphocytic (ALL) and from 0.60 to 2.17 for acute myelocytic leukemia (AML). The combined effect regarding the association of maternal smoking (any vs. no) and leukemia risk was 1.03 for ALL (95% CI = 0.95-1.12, random effects model) and 0.99 for AML (95% CI = 0.90-1.09, fixed effects model). The results remained unchanged when sensitivity analyses were undertaken of studies reporting same maternal smoking periods, those focusing only on childhood leukemia deaths or investigations which did not clearly define AML subtype. The findings of the meta-analysis challenge the limits of traditional epidemiology to provide sound inferences when point estimates of constituent studies range around the null. In particular, this study provides no support to a hypothesis linking maternal smoking during pregnancy with subsequent development of main childhood leukemia subtypes. Further investigations employing molecular and genetic epidemiology, however, might be needed in the hope to reveal even minimal risks pertaining individuals with specific susceptibility to tobacco compounds who sustain high environmental exposures prenatally or postnatally.

Advances of extremely low-frequency electromagnetic fields and childhood leukemia research

The increasingly raised morbidity of hematological malignancies have attracted much attention from scientists and clinicians in recent years, especially the childhood leukemia, It has been demonstrated that extremely low-frequency electromagnetic fields is closely related to pediatric leukemia. The extremely lowfrequency electromagnetic fields might change the size, appearance, quantity, chemical state and energy of cellular biological molecules and induce cascade reaction via effects on cell-to-cell signal transduction, cell proliferation and apoptosis, gene expression and DNA damage, etc, subsequently promote the development of childhood leukemia. This paper overviewed the recent advances of relationship between the extremely lowfrequency electromagnetic fields and childhood leukemia. Key words: Childhood leukemia; Electromagnetic fields; Extremely low-frequency electromagnetic fields

Childhood Leukemia and Traffic Air Pollution in Taiwan: Petrol Station Density as an Indicator

To investigate the relationship between traffic air pollution exposure and development of childhood leukemia (14 yr of age or younger), a matched case-control study was conducted using childhood deaths that occurred in Taiwan from 1996 through 2006. Data on all eligible childhood leukemia deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of children who died from causes other than neoplasms or diseases that were not associated with respiratory complications. The controls were pair matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on the number of petrol stations in study municipalities were collected from the two major petroleum supply companies, Chinese Petroleum Corporation (CPC) and Formosa Petrochemical Corporation (FPCC). The petrol station density (per square kilometer) (PSD) for study municipalities ...

Irradiation-induced p53 expression is attenuated in cells with NQO1 C465T polymorphism.

NAD(P)H:quinone acceptor oxidoreductase (NQO) 1 polymorphism is associated with various hematological malignancies, especially infant leukemia or therapy-related leukemias, which involve the rearrangement of mixed lineage leukemia (MLL) gene. Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (EBV-LCLs) with either of 2 well known polymorphic variations of C609T and C465T were selected from our archives of EBV-LCL clones and studied the induction of p53 expression after DNA damage. Irradiation of cells with C609T/C609T polymorphism (NQO1 *2*2) did not affect the induction of p53 expression. However, irradiation of cells with C465T/WT polymorphism (NQO1 *1*3) resulted in attenuation of p53 and p21 induction. Our results suggest that increased risk of infant leukemia development in patients with NQO1 *1*3 polymorphism is partially dependent on the inhibition of p53 pathway, though further studies are needed to fully understand the pathological role of C465T variant in the development of childhood leukemia.

Childhood Leukemia and Traffic Air Pollution in Taiwan: Petrol Station Density as an Indicator

To investigate the relationship between traffic air pollution exposure and development of childhood leukemia (14 yr of age or younger), a matched case-control study was conducted using childhood deaths that occurred in Taiwan from 1996 through 2006. Data on all eligible childhood leukemia deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of children who died from causes other than neoplasms or diseases that were not associated with respiratory complications. The controls were pair matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on the number of petrol stations in study municipalities were collected from the two major petroleum supply companies, Chinese Petroleum Corporation (CPC) and Formosa Petrochemical Corporation (FPCC). The petrol station density (per square kilometer) (PSD) for study municipalities was used as an indicator of a subject's exposure to benzene and other hydrocarbons present in evaporative losses of petrol or to air emissions from motor vehicles. The subjects were divided into tertiles according to PSD in their residential municipality. The results showed that there was a significant exposure-response relationship between PSD and the risk of leukemia development in young children after controlling for possible confounders. The findings of this study warrant further investigation of the role of traffic air pollution exposure in the etiology of childhood leukemia.

Genome-Wide Scanning of Epigenomic Alterations in Childhood Leukemia

To study how epigenetic changes contribute to childhood leukemia, and to identify new disease biomarkers, we combined an approach of pharmacologic inhibition of epigenetic modifications of chromatin with gene expression arrays (Affymetrix Exon 1.0; and miRNA array, UCSF-designed) to reveal precise epigenetic aberrations on a global scale in defined subsets of leukemia cell lines that recapitulate common genetic subtypes of leukemia. From these analyses, we identified >200 genes up-regulated by 5-aza-2′-deoxycytidine and trichostatin A treatment (including genes encoding both mRNA and miRNA). We validated 50 selected genes using real-time quantitative PCR. We also tested promoter regions for methylation in the cell lines and selected pediatric leukemia bone marrows using bisulfite-DNA sequencing. A panel of leukemia-specific methylation targets was discovered, which includes some well-known genes (such as HOXA5 and DAPK) and several novel candidates in childhood leukemia (eg., CD82 and KLF4). To extend these observations, we performed methylation microarrays on DNA samples isolated from the studied cell lines as well as bone marrows of 35 childhood leukemia patients with defined cytogenetics, using Illumina Methylation Cancer Panel I. This panel includes a total of 1,505 CpG loci from 807 genes. We also assayed corresponding archived newborn bloods (Guthrie cards) from 32 cases, and 19 control Guthrie cards of children matched to the cases based on gender and age, to guage the impact of congenital methylation events on childhood leukemia. Many targets genes, including known tumor suppressor genes and genes involved in DNA repair, cell cycle control and differentiation were found to be methylated in leukemia cell lines and the leukemic bone marrow samples, but not in Guthrie card controls. In addition, the methylation status of a core group of 67 CpG sites can differentiate the common subtypes of childhood leukemia – those with TEL-AML1, E2A-PBX1, high hyperdiploidy, and normal karyotypes. Several genes concordantly methylated in Guthrie cards and leukemic bone marrow may represent prenatal epimutations. With the integration of such assays, we have constructed a panel of potential candidate genes and miRNAs involved in development of childhood leukemia which have aberrant promoter methylation. Our studies lay a foundation for a comprehensive understanding of the full extent of epigenetic changes in development of childhood leukemia and how they may be exploited for therapeutic purposes as well as for early detection of this disease.

Childhood Leukemia Development and Correlation with Traffic Air Pollution in Taiwan using Nitrogen Dioxide as an Air Pollutant Marker

To investigate the relationship between traffic air pollution and development of childhood leukemia (14 yr of age or younger), studies were conducted on a matched cancer case-control cohort using childhood deaths that occurred in Taiwan from 1995 through 2005. Data on all eligible childhood leukemia deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of children who died from causes other than neoplasms or from diseases that were not associated with respiratory complications. The controls were pair matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Air quality data for recorded concentrations of nitrogen dioxide (NO2) from study municipalities for 1995–2005 were obtained as an indicator of a subject's exposure to air emissions from motor vehicles. The subjects were divided into tertiles according to the levels of NO2 in their residential municipality. The results showed that there was a significant exposure-response relationship between exposure to traffic exhaust pollutants and the risk of leukemia among young children after controlling for possible confounders. The findings of this study warrant further investigation of the role of traffic air pollution in the etiology of childhood leukemia.

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia.

Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C-->T) and 1,298 (A-->C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15-0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07--0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20--1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia.

The Woman Who Knew Too Much: Alice Stewart and the Secrets of Radiation (review)

For the past twenty years, most American and British obstetricians have avoided taking routine X rays of patients who are pregnant. In dental offices, at least in the United States, no one is X-rayed without first donning a protective apron extending from shoulders to knees. These precautions are the result, at least in part, of research performed by the British physician and epidemiologist Alice Stewart (b. 1906). Gayle Green's lively biography traces the life of Dr. Stewart, principal discoverer of the link between in utero X-ray exposure and the development of childhood leukemia.

The Influence of Long-Term Exposure of Mice to Randomly Varied Power Frequency Magnetic Fields on Their Nocturnal Melatonin Secretion Patterns

Disruption of the normal melatonin rhythm has many implications in health and disease. Exposure to magnetic fields is alleged to suppress nocturnal melatonin production, which could implicate magnetic fields in the development of, for example, breast cancer. Magnetic fields of overhead powerlines allegedly pose a risk in the development of childhood leukemia, and the question arises whether changed pineal function could play a role here. In this study two strains of mice were exposed to a rms 50-Hz magnetic field which varied randomly between 0.5 and 77 μT with an average of 2.75 μT and compared to sham-exposed groups. The male mice were exposed for 24 h per day from conception until adult age. Nighttime plasma melatonin values were determined using radioimmunoassay (n=9 for each time point). Statistical comparison was done by nonparametric 95% confidence intervals for median differences to determine nocturnal elevated melatonin values. Although a shortcoming of the study was the small sample size, no statistically significant difference in the nocturnal median elevated melatonin values between exposed and sham-exposed groups could be demonstrated. Long-term and continuous exposure to simulated powerline magnetic fields did not result in a decreased nocturnal melatonin secretion in mice.