Childhood cancer and paternal exposure to lonizing radiation: Preliminary findings from the oxford survey of childhood cancers

Paternal occupational data already collected as part of the Oxford Survey of Childhood Cancers have been reviewed. Information on occupations during or before the relevant pregnancy was sought for 15,279 children dying from cancer in England, Wales, and Scotland in the period 1953–81, and for an equal number of matched controls. Estimates were made for paternal exposure to human-made external ionizing radiation in the six months before conception of the survey child—as judged from job histories and dates of birth. Assessments were also made for potential exposure to unsealed sources of radionuclides. Of the eight fathers placed in the highest dose group (≥10 mSv, external radiation), four were cases and four were controls. For the second dose group (5–9 mSv), the corresponding numbers were eight and four, and for the lowest exposed group (1–4 mSv), they were 55 and 42. There were 27 case fathers with potential exposure to radionuclides and only 10 control fathers. The independent effects of the two radiation variables were assessed by means of multiple logistic regression. Relative risks for estimated doses of external radiation were close to unity, but for radionuclide exposure the relative risk was 2.87 (95% CI + 1.15–7.13). These preliminary findings suggest that paternal exposure to radionuclides is a more likely risk factor for childhood cancer than exposure to external radiation. © 1993 Wiley-Liss, Inc.     

Vascular effects of occupational exposure to low-dose ionizing radiation

Damage to the microcirculation caused by high-dose ionizing radiation is well known but data concerning low-dose exposure are scant and contrasting. We employed capillary microscopy to study dermal microcirculation damage resulting from occupational exposure to ionizing radiation doses lower than 5 rem/year (maximum permissible dose in Italy). We studied 145 physicians (60.7% radiologists, 33.8% orthopedic specialists, 5.5% cardiologists) occupationally exposed to ionizing radiation and a control group of 106 subjects in comparable but different occupations not exposed to ionizing radiation or to other skin hazards. All subjects were administered a clinical protocol and underwent capillary microscopy of the fingernail-fold. Capillary microscopy alterations were classified as absent, mild, moderate, marked and severe. Our data confirm that occupational exposure to low-dose ionizing radiation can lead to morphological and functional alterations of the dermal microcirculation, which can be identified early by capillary microscopy. © 1996 Wiley-Liss, Inc.     

低剂量电离辐射长期接触健康效应研究进展

随着核能的发展及电离辐射的广泛应用,接触低剂量电离辐射的职业人群和公众越来越多,低剂量电离辐射接触对人群健康效应包括致癌、非致癌等研究成为公共卫生领域研究的热点。低剂量电离辐射引起的各种生物效应主要取决于辐射的物理性质、接触时间、剂量和剂量率等。目前关于低剂量电离辐射长期接触对人群的健康效应研究结论尚无一致共识。本文就国内外关于低剂量电离辐射长期接触的健康效应研究进行回顾,为低剂量电离辐射长期接触人群的健康效应、影响机制及防护策略研究等提供科学基础。     

Genomic characterization of a three-dimensional skin model following exposure to ionizing radiation

This study aimed at characterizing the genomic response to low versus moderate doses of ionizing radiation (LDIR versus MDIR) in a three-dimensional (3D) skin model, which exhibits a closer tissue complexity to human skin than monolayer cell cultures. EpiDermFT skin plugs were exposed to 0, 0.1 and 1 Gy doses of X-rays and harvested at 5 min, 3, 8 and 24 h post-irradiation (post-IR). RNA was interrogated for global gene expression alteration. Our results show that MDIR modulated a larger number of genes over the course of 24 h compared to LDIR. However, immediately and throughout the first 3h post-IR, LDIR modulated a larger number of genes than MDIR, mostly associated with cell–cell signaling and survival promotion. Significant modulation of pathways was detected only at 3 h post-IR in MDIR with induction of genes promoting apoptosis. Collectively, the data show different dynamics in the response to LDIR versus MDIR, especially in cell-cycle distribution. LDIR-exposed tissues showed signs of attempted cell-cycle re-entry as early as 3 h post-IR, but were arrested beyond 8 h at the G1/S checkpoint. At 24 h, cells appeared to accumulate at the G2/M checkpoint. MDIR-exposed tissues did not exhibit a prolonged G1/S arrest but rather a prolonged G2/M arrest, which was sustained at least up to 24 h. By 24 h cells exhibited signs of recovery in both LDIR- and MDIR-exposed tissues. In summary, the most pronounced difference in the initial cellular response to LDIR versus MDIR is the promotion of protection and survival in LDIR versus the promotion of apoptosis in MDIR.     

Leukemia and exposure to ionizing radiation among German uranium miners

BACKGROUND: It is well known that uranium miners are at an increased risk of lung cancer. Whether they also have an increased risk for other cancer sites remains under discussion. The aim of this study was to examine the leukemia risk among miners. METHODS: An individually matched case-control study of former uranium miners in East Germany was conducted with 377 cases and 980 controls. RESULTS: Using conditional logistic regression models, a dose-response relationship between leukemia risk and radon progeny could not be confirmed. Yet, a significantly elevated risk is seen in the category > or = 400 mSv when combining gamma-radiation and long-lived radionuclides. CONCLUSIONS: The results suggest that an elevated risk for leukemia is restricted to employees with a very long occupational career in underground uranium mining or uranium processing. Moreover, the study does not support the hypothesis of an association between exposure to short-lived radon progeny and leukemia risk.     

An investigation of the effect of paternal occupation group at conception on birth weight and gestational age

The occupational histories of fathers were collected prospectively as part of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), and were used to investigate the association of paternal job title with a baby's birth weight and gestational age. The analysis cohort consisted of 4,795 singleton live-born babies whose fathers responded fully to questionnaire items regarding occupational history. Jobs were coded using the British Standard Occupational Codes and classified into nine major occupational groups. A 73-gram difference (95% CI: 0.16, 145.17) was found between the mean birth weight of full-term babies born of professional fathers (3,543 gm) and of fathers working in craft and related occupations (3,470 gm). This difference decreased and lost significance after controlling for sociodemographic variables. No difference was found in the mean birth weight of preterm babies, or in the rate of preterm delivery, when analyzed by paternal occupation at conception. Our results suggest that when important sociodemographic variables are known, the father's job title alone may not be a useful predictor of birth weight or preterm delivery. Am. J. Ind. Med. 31:738–743, 1997. © 1997 Wiley-Liss, Inc.     

The risk of childhood cancer from intrauterine and preconceptional exposure to ionizing radiation.

The findings of studies investigating whether exposures to ionizing radiation before birth, either pre- or post-conception, increase the risk of childhood cancer have provoked much scientific controversy. An epidemiological association between the abdominal exposure of pregnant women to diagnostic X-rays and childhood cancer was first reported in the 1950s, while an association between the recorded dose of radiation received occupationally by fathers before the conception of their offspring and childhood leukemia was reported only recently in 1990. The scientific interpretation of these particular statistical associations is by no means straightforward, but the latest analyses of intrauterine irradiation and childhood cancer indicate that a causal inference is likely. Scientific committees have adopted risk coefficients for the intrauterine exposure of somatic tissues, which for childhood leukemia are comparable to those accepted for exposure in infancy, although questions remain about the level of risk of childhood solid tumors imparted by exposure to radiation in utero and shortly after birth. In contrast, the association between paternal preconceptional radiation dose and childhood leukemia has not been confirmed by studies using objectively determined doses. The original association has been found to be restricted to children born in one village, it does not extend to cancers other than leukemia, and it is markedly inconsistent with the established body of knowledge on radiation-induced hereditary disease. A causal interpretation of this association has effectively been abandoned by scientific authorities.     

电离辐射心血管系统损伤途径的研究进展

不同剂量电离辐射对心血管系统的损伤途径存在一定差异,高剂量电离辐射可直接破坏微血管内皮细胞功能屏障,影响细胞黏附分子(cell adhesion molecules,CAMs)等生物大分子的表达,诱导炎性细胞渗出、组织纤维化及坏死等慢性微血管内皮细胞损伤。进而影响循环系统内环境稳态,诱发早期心血管疾病。小剂量电离辐射对心血管系统的损伤途径主要表现为电离辐射的异常DNA甲基化效应和氧化应激效应,由此产生的代谢产物如活性氧自由基(reactive oxygen species, ROS)和同型半胱氨酸(homocysteine, Hcy)均可对心血管系统造成慢性损伤,电离辐射持续暴露导致次级效应代谢产物的蓄积将加剧心血管系统损伤倾向。     

The evolution of attitudes to the human hazards of ionizing radiation and to its investigators.

Hanford Works, Richland, Washington, was one of the largest atomic plants in the United States. Several tens of thousands of persons employed at that site have been followed over four decades. Impressive as this number may seem at first sight, the Mancuso/Stewart/Kneale team consider it too small to estimate a cancer risk even 10 times as large as the low level radiation estimate produced by the International Commission on Radiation Protection [Stewart and Kneale, 1981]. It has been estimated [Stern, 1981] that a population 10–100 times the size would be required, even employing sophisticated techniques of analysis.     

Occupational exposure to ionizing and non-ionizing radiation and risk of glioma

BACKGROUND: Although the aetiology of glioma is poorly understood, the higher incidence in males has long suggested an occupational cause. AIM: To investigate possible associations between occupational exposure to ionizing, ultraviolet (UV), radiofrequency (RF) and extremely low frequency (ELF) radiation and adult glioma risk. METHODS: Case-control study using histologically confirmed cases of glioma first diagnosed between 1987 and 1991 in Melbourne, Australia, matched by age, sex and postcode of residence. A detailed occupational history was obtained for each subject. Exposure to radiation was assessed using a Finnish job exposure matrix (FINJEM) for all the radiation types as well as self-reports and expert hygienist review for RF and ionizing radiation. For ELF and UV, gender-specific FINJEM analysis was performed. RESULTS: The study population consisted of 416 cases of glioma and 422 controls. The risk estimates given by FINJEM for ELF, RF and ionizing radiation were close to or below unity. Gender-specific analysis for UV showed odds ratios of 1.60 [95% confidence interval (CI) 0.95-2.69] and 0.54 (95% CI 0.27-1.07) for the highest exposed group of men and women, respectively (corresponding P value for trend was 0.03 and 0.04). CONCLUSIONS: We did not find evidence of an association between glioma and occupational exposure to ELF, RF and ionizing radiation. UV radiation was associated with increased glioma risk for men but this result could have been confounded by other predominantly male occupational and lifestyle exposures associated with high UV. Further investigation of UV radiation and glioma risk is suggested.     

Occupational exposure to ionizing and non-ionizing radiation and risk of non-Hodgkin lymphoma

Objective To investigate the association between occupational exposure to ionizing, ultraviolet (UV), radiofrequency (RF) and extremely low frequency (ELF) radiation and risk of developing non-Hodgkin lymphoma (NHL) in a population-based case-control study. Methods The study population consisted of 694 NHL cases, first diagnosed between 1 January 2000 and 31 August 2001, and 694 controls from two regions in Australia, matched by age, sex and region of residence. A detailed occupation history was first obtained using a lifetime calendar and a telephone interview. Exposure to radiation was then assessed using a Finnish job-exposure matrix (FINJEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models that included the matching variables as covariates. Results For ionizing radiation, the ORs were close to unity. For UV and ELF radiation, the highest exposed group of workers had ORs of 1.32 (95% CI = 0.96–1.81) and 1.25 (95% CI = 0.91–1.72), respectively. For UV radiation there was a positive dose–response when exposure was lagged by 5 and 10 years (P for trend 0.04 for both lag periods). Workers in the upper tertile of exposure for RF radiation had an OR of 3.15 (95% CI = 0.63–15.87), but the estimate was based on very small numbers. Conclusions Our results do not provide support for an association between NHL and occupational exposure to ionizing or ELF radiation. For UV radiation, our findings are consistent with a weak positive association. Further investigation focusing on UV and RF radiation and NHL is required.     

A novel in vitro survival assay of small intestinal stem cells after exposure to ionizing radiation

The microcolony assay developed by Withers and Elkind has been a gold standard to assess the surviving fraction of small intestinal stem cells after exposure to high (≥8 Gy) doses of ionizing radiation (IR), but is not applicable in cases of exposure to lower doses. Here, we developed a novel in vitro assay that enables assessment of the surviving fraction of small intestinal stem cells after exposure to lower IR doses. The assay includes in vitro culture of small intestinal stem cells, which allows the stem cells to develop into epithelial organoids containing all four differentiated cell types of the small intestine. We used Lgr5-EGFP-IRES-CreERT2/ROSA26-tdTomato mice to identify Lgr5⁺ stem cells and their progeny. Enzymatically dissociated single crypt cells from the duodenum and jejunum of mice were irradiated with 7.25, 29, 101, 304, 1000, 2000 and 4000 mGy of X-rays immediately after plating, and the number of organoids was counted on Day 12. Organoid-forming efficiency of irradiated cells relative to that of unirradiated controls was defined as the surviving fraction of stem cells. We observed a significant decrease in the surviving fraction of stem cells at ≥1000 mGy. Moreover, fluorescence-activated cell sorting analyses and passage of the organoids revealed that proliferation of stem cells surviving IR is significantly potentiated. Together, the present study demonstrates that the in vitro assay is useful for quantitatively assessing the surviving fraction of small intestinal stem cells after exposure to lower doses of IR as compared with previous examinations using the microcolony assay.     

孕前父亲烟草暴露与6岁儿童智力水平的前瞻性队列研究

目的 评估孕前父亲烟草暴露对6岁儿童智力的影响,为指导优生优育服务提供循证依据。方法 本研究纳入2012年建立的上海闵行出生队列的530对母子,在孕妇建大卡时通过结构式问卷获得了孕前3个月父亲烟草暴露情况,在儿童6岁时利用第四版《儿童韦氏智力测试量表》中文版简版考察儿童智力水平。采用多因素线性回归模型分析孕前父亲烟草暴露对6岁儿童智力水平的影响。结果 调整协变量后,孕前父亲烟草暴露使儿童总智商下降2.83分(95%CI:-5.51～-0.16),其中孕前父亲吸烟的效应值(OR=3.15,95%CI:-6.32～0.03)略高于孕前父亲二手烟暴露(OR=2.62,95%CI:-5.54～0.30)。孕前父亲吸烟对儿童总智商和知觉推理的影响呈剂量反应关系(趋势检验P<0.05),父亲每天吸烟5支以上的儿童,总智商下降6.57分(95%CI:-10.88～-2.26),知觉推理下降5.83分(95%CI:-10.61～-1.05)。此外,儿童性别和胎龄与孕前父亲烟草暴露在对儿童智商的影响中表现出显著的交互作用(P<0.05),即父亲烟草暴露对女童、胎龄<39周的儿童的智力影响更强。结论 本研究发现孕前3个月父亲的烟草暴露与6岁儿童智力水平的下降有关,提示孕前健康指导应加强对备孕期间丈夫控烟的宣传,倡导夫妻双方共同承担起优生优育的责任。     

Household exposure to pesticides and risk of childhood acute leukaemia

Objectives

To investigate the relation between childhood acute leukaemia and household exposure to pesticides.

Methods

The study included 280 incident cases of acute leukaemia and 288 controls frequency matched on gender, age, hospital, and ethnic origin. The data were obtained from standardised face to face interviews of the mothers with detailed questions on parental occupational history, home and garden insecticide use, and insecticidal treatment of pediculosis. Odds ratios were estimated using unconditional regression models including the stratification variables parental socioeconomic status and housing characteristics.

Results

Acute leukaemia was observed to be significantly associated with maternal home insecticide use during pregnancy (OR = 1.8, 95% CI 1.2 to 2.8) and during childhood (OR = 1.7, 95% CI 1.1 to 2.4), with garden insecticide use (OR = 2.4, 95% CI 1.3 to 4.3), and fungicide use (OR = 2.5, 95% CI 1.0 to 6.2) during childhood. Insecticidal shampoo treatment of pediculosis was also associated with childhood acute leukaemia (OR = 1.9, 95% CI 1.2 to 3.3).

Conclusion

The results reported herein support the hypothesis that various types of insecticide exposure may be a risk factor for childhood acute leukaemia. The observed association with insecticidal shampoo treatment of pediculosis, which has never been investigated before, requires further study.     

Mortality of workers exposed to ionizing radiation at the French National Electricity Company

BACKGROUND: Exposure to ionizing radiation increases the risk of cancer in humans. Nuclear workers receive low doses over a relatively long period of time. METHODS: A mortality study of a cohort of workers exposed to ionizing radiation at Electricité de France (EDF) was conducted. The cohort consisted of 22,395 individuals monitored for radiation exposure between 1961 and 1994, and followed-up for an average of 11.7 years. RESULTS: Our study demonstrates a clear healthy worker effect (HWE) since mortality is less than half what is expected from National mortality statistics. The HWE is greater among workers who have spent most of their career in the nuclear sector. The analysis by cancer site shows no excess compared with the general population. No significant trend was observed according to level of exposure to ionizing radiation. CONCLUSIONS: The mortality of workers exposed to ionizing radiation at the French National Electricity company is very low compared to the French national mortality.     

职业暴露低剂量电离辐射人群细胞遗传学损伤及受照剂量的研究

目的对放射工作者个人累积受照剂量、健康效应指标、细胞遗传学指标进行检测,探索长期低剂量辐射对工作者健康的影响。方法暴露组配戴“TLDmodel 469”个人剂量监测计,用“TLP-热释光剂量数据处理系统”测读结果。微量全血培养法检测染色体畸变及微核。询问病史、自觉症状,检查内科、皮肤科、眼科、五官科,检验WBC DC、W-LCR、W-SCR、Hb、PLT、ALT、HB-sAg。结果暴露组受照剂量最高192.02 mSv/a,最低0.42 mSv/a,人均年受照剂量5.47 mSv/a。暴露组中有头疼、头晕、易倦、乏力、嗜睡、记忆力减退等者占13.47%,高于对照组5.79%。暴露组眼晶状体混浊发生率为32.42%(709/2 187),显著高于对照组的6.25%(15/240)。暴露组染色体总畸变率1.61%,高于对照组0.16%。受照剂量与染色体总畸变率呈正相关关系(r=0.982,P<0.01),与染色体细胞畸变率呈正相关关系(r=0.978,P<0.01)。同位素组、介入放射组高于其他组(χ2=565.54、496.12,P<0.01)。结论用改良微量全血培养法检测放射工作者染色体型畸变超过2%,双着丝粒体≥1%,应考虑诊断慢性放射病。     

Parental marijuana use and risk of childhood acute myeloid leukaemia: a report from the Children's Cancer Group (United States and Canada)

The aetiology of childhood acute myeloid leukaemia (AML) is largely unknown. Maternal marijuana use just before, or during pregnancy has been previously associated with childhood AML. This case-control investigation formally tested the hypothesis that parental marijuana use increases the risk of childhood AML in offspring. Incident cases of AML <18 years of age, diagnosed between 1989 and 1993, and registered with the Children's Cancer Group (a paediatric clinical co-operative group), were eligible for inclusion. Control children were selected via random digit dialling and individually matched 1:1 to cases on age, race and residential location, except for rare morphological subtypes that were matched 1:2. Parental telephone interviews were conducted to determine exposure and covariate information. Conditional logistic regression was used to estimate matched odds ratios (OR) and 95% confidence intervals [CI] adjusted for household income, parental education and parental age. The analysis included 517 cases and 610 matched controls. A series of sensitivity analyses examined the potential for recall bias. Ever lifetime use of marijuana by mothers was not associated with childhood AML [OR = 0.89; 95% CI = 0.66, 1.19]. Maternal marijuana use any time during the 3 months before, or during pregnancy was inversely associated with childhood AML [OR = 0.43; 95% CI = 0.23, 0.80]. Paternal use during the same time period was not associated with risk. Assuming a large degree of differential exposure misclassification was present, the corrected ORs ranged between 0.82 and 1.40. The previously reported positive association between maternal marijuana use before or during pregnancy and childhood AML was not confirmed. The decreased ORs observed in this study may be due to recall bias assuming plausibly low values of sensitivity.