Possible carcinogenic effects of X-rays in a transgenerational study with CBA mice.
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A lifetime experiment using 4279 CBA/J mice was carried out to investigate whether the pre-conceptual exposure of sperm cells to X-ray radiation or urethane would result in an increased cancer risk in the untreated progeny, and/or increased susceptibility to cancer following exposure to a promoting agent. The study consisted of four main groups, namely a control group (saline), a urethane group (1 mg/g body wt) and two X-ray radiation groups (1 Gy, 2 Gy). At 1, 3 and 9 weeks after treatment, the males of these four parental groups were mated with untreated virgin females. The offspring of each parental group was divided into two subgroups: one received s.c. urethane (0.1 mg/g body wt once) as a promoter, the other saline, at the age of 6 weeks. All animals were evaluated for the occurrence of tumours. K-ras oncogene and p53 tumour suppressor gene mutations were investigated in frozen lung tumour samples. The female offspring of male parents exposed to X-rays 1 week before their mating showed a trend towards a higher tumour incidence of the haematopoietic system than the F1 controls. In addition, a higher percentage of bronchioloalveolar adenocarcinomas in male offspring born to irradiated paternals mated 1 week after X-ray treatment points to a plausible increased sensitivity of post-meiotic germ cell stages towards transgenerational carcinogenic effects. On the other hand, no increased tumour incidence and malignancy were observed in the offspring born to irradiated paternals mated 3 and 9 weeks after X-ray treatment. Paternal urethane treatment 1, 3 and 9 weeks prior to conception did not result in significantly altered incidence or malignancy of tumours of the lung, liver and haematopoietic tissue in the offspring. K-ras mutations increased during tumour progression from bronchioloalveolar hyperplasia to adenoma. Codon 61 K-ras mutations were more frequent in lung tumours of urethane-promoted progeny from irradiated parents than from control parents. P53 mutations were absent from these lung alterations. (+info)
Environmental semen studies--is infertility increased by a decline in sperm count?
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The objective of the studies was to evaluate infertility according to sperm count shifts. The distribution of the sperm count of 1024 Danish men (median 56 million/ml) served as reference. The data were transformed with multiplicative or additive models to create alternative distributions with median sperm count values changed by 25-100%. Sperm-count-specific fecundabilities were provided from a follow-up of first-pregnancy planners in a Danish population. The estimated average fecundability of the 1024 Danish men was 16.9% [95% confidence interval (95% CI) 16.7-17.2], and the proportion of cohabiting men with spouses pregnant within 1 year was 86.0% (95% CI 84.1-87.8). Simulations of alternative sperm count distributions indicated that the relationship between sperm count shift and fertility strongly depends on the median level of the sperm count at onset and the type of shift, a dramatic decline from a high level in a multiplicative model indicating a marginal change and a minor decline from a low level in an additive model representing a strong decrease in fertility. In some cases sperm count, therefore, may be an early warning of changes in fertility. (+info)
Objectives, designs and populations of the European Asclepios study on occupational hazards to male reproductive capability.
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The main objective of the Asclepios program was to examine occupational risk factors for the male reproductive system. The program focused on occupational exposure to fungicides (farmers, greenhouse workers, and vineyard workers), styrene (laminators in the reinforced plastics industry) and inorganic lead (battery workers, foundry workers, and lead smelters). Questionnaire studies of time to pregnancy were combined with longitudinal and cross-sectional studies of semen quality. The 8 data-collecting centers addressed 6553 male workers and contributed time-to-pregnancy values on the 3077 most recent pregnancies. Data collection was by interview or self-collection. The average response rate across all exposures and centers was 69.8%. The Asclepios project is the first international multicenter research project on environmental risks to male reproductive function. A protocol for epidemiologic research on occupational risk factors to the male reproductive system was developed, and links between epidemiologic and experimental units were established. The majority, but not all, of the studies was completed within the given time frame. (+info)
Cancer in children of nuclear industry employees: report on children aged under 25 years from nuclear industry family study.
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OBJECTIVE: To determine whether children of men and women occupationally exposed to ionising radiation are at increased risk of developing leukaemia or other cancers before their 25th birthday. DESIGN: Cohort study of children of nuclear industry employees. SETTING: Nuclear establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels. SUBJECTS: 39 557 children of male employees and 8883 children of female employees. MAIN OUTCOME MEASURES: Cancer incidence in offspring reported by parents. Employment and radiation monitoring data (including annual external dose) supplied by the nuclear authorities. RESULTS: 111 cancers were reported, of which 28 were leukaemia. The estimated standardised incidence ratios for children of male and female employees who were born in 1965 or later were 98 (95% confidence interval 73 to 129) and 96 (50 to 168) for all malignancies and 109 (61 to 180) and 95 (20 to 277) for leukaemia. The leukaemia rate in children whose fathers had accumulated a preconceptual dose of >/=100 mSv was 5.8 times that in children conceived before their fathers' employment in the nuclear industry (95% confidence interval 1.3 to 24.8) but this was based on only three exposed cases. Two of these cases were included in the west Cumbrian ("Gardner") case-control study. No significant trends were found between increasing dose and leukaemia. CONCLUSIONS: Cancer in young people is rare, and our results are based on small numbers of events. Overall, the findings suggest that the incidence of cancer and leukaemia among children of nuclear industry employees is similar to that in the general population. The possibility that exposure of fathers to relatively high doses of ionising radiation before their child's conception might be related to an increased risk of leukaemia in their offspring could not be disproved, but this result was based on only three cases, two of which have been previously reported. High conceptual doses are rare, and even if the occupational association were causal, the number of leukaemias involved would be small; in this study of over 46 000 children, fewer than three leukaemias could potentially be attributed to such an exposure. (+info)
Effects of pesticide exposure on time to pregnancy: results of a multicenter study in France and Denmark. ASCLEPIOS Study Group.
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The aim of this study was to determine whether there was a relation between male exposure to pesticides and the amount of time needed to conceive (time to pregnancy) for farmers and agricultural workers in France and Denmark. The authors used retrospective studies to compare the time to pregnancy of couples in which the man was exposed to pesticides during the year before the birth of their youngest child with that of couples in which the man was not exposed. In 1995 and 1996, the authors studied 362 French rural workers (142 exposed to pesticides and 220 not exposed), 449 Danish farmers (326 conventional farmers exposed to pesticides and 123 nonexposed organic farmers), and 121 Danish greenhouse workers exposed to pesticides. The fecundability ratio for exposure to pesticides (Cox model, before and after adjustment for confounding factors) did not differ from 1 in any of the three populations. In France, the adjusted fecundability ratio was 1.17 (95% confidence interval (CI) 0.89-1.55) for exposed and nonexposed agricultural workers. In Denmark, it was 1.09 (95% CI 0.82-1.43) for exposed and nonexposed farmers and 0.83 (95% CI 0.69-1.18) for greenhouse workers and nonexposed farmers. Thus, this study found no relation between fertility (time to pregnancy) and male exposure to pesticides. (+info)
Are the children of fathers whose jobs involve contact with many people at an increased risk of leukaemia?
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OBJECTIVES: To investigate the hypothesis that children of men whose jobs involve contact with many people (particularly children) are at an increased risk of leukaemia. METHODS: A population based dataset obtained from routinely collected death certificates involving 14,168 cancer deaths occurring before the age of 15 years registered in England and Wales between 1959-63 and 1970-90. Associations were assessed with the proportional cancer mortality ratio (PCMR), with all childhood cancer deaths forming the standard for comparison. The PCMRs were adjusted, by stratification, for age and year of death (in 1-year bands) and paternal social class (nine categories). Analyses were performed by estimated level of paternal occupational social contact (high, medium, and low) for all leukaemias, leukaemia subtype, age at death, year of death, and individual occupation. RESULTS: Out of 223 occupations, 36 (16%) were identified as having potentially high levels of social contact, and 27 (12%) as having potentially medium levels of social contact. No associations were found between paternal occupational social contact and death during childhood from leukaemia (high social contact: PCMR 94, 95% confidence interval (95% CI) 87 to 102; medium social contact: 101, 95 to 106). No associations were found when the data were analysed by leukaemia subtype, age at death, year of death, or individual occupation. CONCLUSION: The findings presented here do not support the suggestion that childhood leukaemia is related to the amount of social contact that fathers experience at work. (+info)
Low birthweight and prematurity in relation to paternal factors: a study of recurrence.
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BACKGROUND: The importance of paternal determinants in the occurrence of low birthweight and prematurity is not well known. We investigated these outcomes in siblings and paternal half siblings as a function of changes in putative external determinants between two births in fathers who had experienced the birth of a premature and/or low birthweight (PTB/LBW) infant. METHODS: All fathers who, between 1980 and 1992, had an infant born before 37 completed weeks' gestation or weighing <2500 g and a following child were studied. We identified 14 147 pairs of siblings from Danish national registers. The recurrence risk was studied in three sub-cohorts defined by the outcome in the index child (PTB only, PTB/LBW, LBW only). We estimated the recurrence risk in the younger sibling according to changes of female partner, municipality type, occupation, and father's social status. RESULTS: The overall recurrence risk was 16.7% for preterm delivery and 16.8% for LBW. Changing female partner was, as expected, associated with a reduction in the recurrence risk for both outcomes (RR = 0.40; 95% CI: 0.27-0.60 for preterm delivery and RR = 0.38; 95% CI : 0.26-0.56 for LBW). None of the other studied factors was associated with changes in the recurrence risk. Fathers who changed partner had offspring with similar birthweight and gestational length between the three sub-cohorts, while a difference was evident in offspring to fathers whose female partner was unchanged. CONCLUSIONS: We did not identify any paternal factor of importance in the occurrence of LBW and preterm delivery. (+info)
Influence of paternal exposure to oil and oil products on time to pregnancy and spontaneous abortions.
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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. (+info)