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.     

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.     

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.     

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.     

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.     

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.     

低剂量电离辐射暴露者淋巴细胞变化与受照剂量的关系

目的：探讨个人受照剂量对外周血淋巴细胞微核的影响，以采取有效措施，保护放射工作者健康。方法：对放射工作人员个人受照剂量连续4年进行监测，并检验淋巴细胞微核，分析两者相关规律。结果：放射组工作人员淋巴细胞微核率、微核检出率均显著高于对照组。乡镇医院组、工业探伤组显著高于市属医院和县区医院组。淋巴细胞微核率、微核阳性检出率与放射工龄呈曲线正相关关系（r=0．957，P〈0．01）；与个人年受照剂量呈直线正相关（r=0．996，P〈0．01）；与个人累积受照剂量呈直线正相关（r=0．996，P〈0．01）。结论：低剂量电离辐射对放射工作人员细胞遗传物质有一定损伤，放射防护工作中必须重视工作场所和个人防护，减少工作者受照剂量。     

Job factors,radiation and cancer mortality at OAK ridge national Laboratory: Follow-up through 1984

A previous study of mortality among white men hired at Oak Ridge National Laboratory between 1943 and 1972 (n + 8,318) revealed an association between low-dose external penetrating ionizing radiation and cancer mortality in follow-up through 1984. The association was not observed in follow-up through 1977. This report considers the role of possible selection and confounding factors not previously studied. Control for hire during the World War II era and employment duration of less than 1 year had little effect on the radiation risk estimates. Risks associated with length of time spent in 15 job categories were considered as proxies for the effects of other occupational carcinogens. Ajustment for employment duration in each job category one at a time produced only small changes in the radiation risk estimate. Adjustment for potential exposures to beryllium, lead, and mercury also had little effect on the radiation risk estimates. These analyses suggest that selection factors and potential for chemical exposure do not account for the previously noted association of external radiation dose with cancer mortality. However, power to detect effects of chemical exposures is limited by a lack of individual exposure measures. © 1993 Wiley-Liss, Inc.     

Influence of paternal exposure to oil and oil products on time to pregnancy and spontaneous abortions

The objective of this study was to evaluate the influence of exposure to oil and oil products among men on the time taken for their wives to conceive and on the incidence of spontaneous abortion among them. A cross-sectional study was performed by posting questionnaires to 1,269 men employed as offshore mechanics, offshore operators, offshore drilling personnel, car mechanics (the 'exposed' occupations) and carpenters ('unexposed'). The married men were asked to give a separate questionnaire to their wives for details about their pregnancies. The time elapsed between the beginning of coitus without contraception and the wife becoming pregnant (time to pregnancy) was analyzed with Cox regression analysis by calculating fecundability ratios for the pregnancies for the men exposed to oil and oil products as compared with the men who were not exposed. Spontaneous abortions were analyzed with logistic regression by calculating odds ratios for the pregnancies in which the men were exposed vs. not exposed. A total of 741 (58%) men returned the questionnaires. A total of 301 pregnancies were analyzed for time taken to conceive and 580 for spontaneous abortion. The results were adjusted for variables that could significantly influence conception time (previous infections of the reproductive system and coffee drinking) or the incidence of spontaneous abortion (mother's age, parity and smoking). The outcomes between the exposed and unexposed pregnancies showed no significant differences. Car mechanics had a lower fecundability ratio before 1992 than after 1992. Paternal exposure to hydrocarbons in the occupations studied did not seem to have had a major influence on time to conception or the incidence of spontaneous abortion among the wives of the men exposed to oil products.     

Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case-control study based on death certificates

OBJECTIVES—To explore whether mortality from multiple sclerosis is negatively associated with exposure to sunlight.
METHODS—Two case-control studies based on death certificates were conducted for mortality from multiple sclerosis and non-melanoma skin cancer (as a positive control) to examine associations with residential and occupational exposure to sunlight. Cases were all deaths from multiple sclerosis between 1984 and 1995 in 24 states of the United States. Controls, which were age frequency matched to a series of cases, excluded cancer and certain neurological deaths. The effects of occupational exposure to sunlight were assessed among subjects with usual occupations requiring substantial activity, so as to exclude those whose indoor jobs resulted from disabilities subsequent to the onset of the disease. Multiple logistic regression analyses were applied, with adjustment for age, sex, race, and socioeconomic status.
RESULTS—Unlike mortality from skin cancer, mortality from multiple sclerosis was negatively associated with residential exposure to sunlight (odds ratio (OR)=0.53 (multiple sclerosis) and OR=1.24 (skin cancer)). Odds ratios for the highest occupational exposure to sunlight were 0.74 (95% confidence interval (95% CI) 0.61 to 0.89) for mortality from multiple sclerosis, compared with 1.21 (1.09 to 1.34) for mortality from non-melanoma skin cancer. The OR was 0.24 for the combined effect of the highest levels of residential and occupational exposure to sunlight on multiple sclerosis, compared with an OR of 1.38 for skin cancer.
CONCLUSIONS—In this exploratory study, mortality from multiple sclerosis, unlike mortality from skin cancer, was negatively associated with both residential and occupational exposure to sunlight.


Keywords: multiple sclerosis; aetiology; latitude; ultraviolet radiation; sunlight; occupation; residence; skin cancer     

Long-term occupational lead exposure,chronic nephropathy,and renal cancer: A case report

The case of a 61 -year-old male with repeated episodes of overt clinical lead poisoning and courses of chelation therapy during his 34 years of employment in a secondary lead smelter is presented. Renal function impairment with elevated serum creatinine and blood urea nitrogen and with markedly reduced glomerular filtration rate was detected several years before the discovery of a clear cell adenocarcinoma of the right kidney. After successful surgical removal of the tumor, the patient's renal function continued its previous trend of slow deterioration.     

A cross-sectional investigation of chronic exposure to microcystin in relationship to childhood liver damage in the Three Gorges Reservoir Region, China

Background: Microcystin-producing Microcystis bloom is a severe water problem in the world. Some reports indicate that chronic exposure to microcystin may result in liver damage in adults, but information on effects in children is limited.Objective: We investigated the relationship between microcystin exposure and liver damage in children.Methods: We measured microcystin concentrations in drinking water and aquatic food (carp and duck) from two lakes and four wells. Participants were 1,322 children 7–15 years of age who obtained drinking water from one of the tested sources, completed questionnaires, and provided blood samples for serum liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT)] and serum microcystin analysis. Multivariable logistic regression was used to identify risk factors associated with liver damage (two or more abnormal serum enzyme levels in ALT, AST, ALP, or GGT).Results: Microcystin was detected in most samples of water and aquatic food from two lakes. Children who drank water from the lake with the highest microcystin concentrations had a total estimated daily microcystin intake of 2.03 μg, a value much higher than the tolerable daily intake (0.40 μg) proposed by the World Health Organization for children. Hepatitis B virus (HBV) infection, use of hepatotoxic medicines, and microcystin exposure were associated with liver damage. AST and ALP levels were significantly higher in high-microcystin-exposed children than in low-exposed children and unexposed children when participants who were HBV-positive or hepatotoxic medicine users were excluded from the analysis.Conclusion: These results suggest that chronic exposure to microcystin may be associated with liver damage in children in the Three Gorges Reservoir Region.     

Prevention of work-related injuries and diseases: lessons from experience with ionizing radiation

Almost immediately after the discovery of the Roentgen ray, in 1895, radiation injuries of various kinds began to be encountered in early X-ray workers, radium handlers, radiologists, and exposed patients. The injuries, which were predominantly acute reactions resulting from the killing of cells in affected tissues, were found to be preventable merely by keeping exposures below relevant threshold levels. By the middle of the twentieth century, however, it was realized that thresholds might not exist for certain effects of ionizing radiation, such as mutagenic, carcinogenic, and teratogenic effects. The risks of such effects in workers and other populations exposed to low-level radiation have thus been of increasing concern in recent years. The scientific basis for assessing such risks and the principles that have evolved for their control have important implications for occupational and environmental health in general.