Paternal Preconceptional Irradiation Research Articles

Childhood cancer research in oxford III: The work of CCRG on ionising radiation

BackgroundHigh doses of ionising radiation are a known cause of childhood cancer and great public and professional interest attaches to possible links between childhood cancer and lower doses, particularly of man-made radiation. This paper describes work done by the Childhood Cancer Research Group (CCRG) on this topicMethodsMost UK investigations have made use of the National Registry of Childhood Tumours and associated controls. Epidemiological investigations have included national incidence and mortality analyses, geographical investigations, record linkage and case-control studies. Dosimetric studies use biokinetic and dosimetric modelling.ResultsThis paper reviews the work of the CCRG on the association between exposure to ionising radiation and childhood cancer, 1975–2014.ConclusionThe work of CCRG has been influential in developing understanding of the causes of 'clusters' of childhood cancer and the risks arising from exposure to ionising radiation both natural and man-made. Some clusters around nuclear installations have certainly been observed, but ionising radiation does not seem to be a plausible cause. The group’s work has also been instrumental in discounting the hypothesis that paternal preconception irradiation was a cause of childhood cancers and has demonstrated an increased leukaemia risk for children exposed to higher levels of natural gamma-ray radiation.

Ionizing Radiation and Childhood Leukemia

I read with interest the recent review by Belson et al. (2007) on childhood leukemia, particularly the sections dealing with radiation exposure. Like the authors, I believe that ionizing radiation is strongly associated with childhood acute leukemia. I would like to point out that several critical pieces of information were overlooked; these support stronger and more meaningful conclusions. Although atomic bomb survivors offer the clearest evidence of leukemia risk after childhood exposures to ionizing radiation, studies of children exposed to fallout in other contexts should not be downplayed. Belson et al. (2007) stated that “radiation exposure secondary to the Chernobyl accident has not been shown to increase the risk of leukemia in children who were exposed after birth …,” but they failed to mention the case–control study of Noshchenko et al. (2002), which found significant increases in childhood and acute leukemias in association with estimated childhood exposures. Children living downwind of the Nevada Test Site have also shown a significant increase in leukemia related to estimated fallout exposure (Stevens et al. 1990). In utero exposure to ionizing radiation has been a known causal factor for childhood cancer for > 50 years. Although Belson et al. (2007) stated that the lack of evidence for a childhood leukemia risk among atomic bomb survivors constitutes the “most notable reason for doubt of a true association,” they overlooked the reviews of Wakeford and Little (2002, 2003); these authors demonstrated that the highly uncertain atomic bomb survivor data are statistically compatible with the robust set of data found in the Oxford Survey of Childhood Cancers and related X-ray exposure cohorts. There is no valid reason to doubt this association at present. The association between preconception paternal irradiation (PPI) and childhood leukemia has always been controversial. Two of the major objections to the “Gardner hypothesis,” as Belson et al. (2007) pointed out, have been mixed evidence from studies of radiation-exposed fathers and a lack of positive evidence in the children of the atomic bomb survivors. Regarding the first objection, Belson et al. overlooked the two largest studies of the children of radiation workers. Draper et al. (1997) conducted a UK-wide case–control study of childhood cancers in relation to paternal radiation exposure. This study showed, based on > 13,000 cases not included in the study of Gardner et al. (1990), that children with leukemia or non-Hodgkin lymphoma were significantly more likely than controls to have fathers who were radiation workers. Dickinson and Parker (2002) conducted a cohort study of > 250,000 births in Cumbria, England, including the cases of Gardner et al. (1990), and found a significant 2-fold increase in the risk of leukemia and non-Hodgkin lymphoma among the children of radiation workers. These and other studies, taken together, give statistical support to the idea that paternal radiation work is a risk factor for childhood leukemia. When interpreting the evidence for a PPI effect in atomic bomb survivors, it is important to consider what is known about potential mechanisms. As reviewed by Niwa (2003), Nomura (2003), and others, animal studies have consistently demonstrated that PPI can cause or increase the susceptibility to leukemia in offspring. In addition to fascinating evidence of postconception genomic instability after preconception exposure, many studies suggest that there may a window of sensitivity corresponding to post-meiotic stages of spermatogenesis; in humans, this would mean the few months leading up to conception (Adler 1996). Of the roughly 30,000 children of atomic bomb survivors, only about 2% were conceived in the 6 months after the bombings. Based on the spontaneous leukemia rate reported by Yoshimoto (1990), the expected number of spontaneous cases in this subcohort would be < 1, and an excess on the order suggested by the radiation worker studies would not be statistically apparent. For this and other reasons, the atomic bomb survivors may not be an appropriate comparison group. To summarize, it is not unreasonable to observe that the weight of evidence generated to date supports the idea that preconception, prenatal, and postnatal exposures to ionizing radiation are all risk factors for childhood leukemia.

New germline mutations in the hypervariable minisatellite CEB1 in the parents of children with leukaemia

Gardner and co-workers advanced the hypothesis that the Seascale leukaemia cluster could have been caused by new mutations in germ cells, induced by paternal preconceptional irradiation (PPI) exposure at the Sellafield nuclear installation. Since evidence has shown that PPI can increase the de novo germline mutation rate in hypervariable minisatellite loci, we investigated the hypothesis that sporadic childhood leukaemia might be associated with an increased parental germline minisatellite mutation rate. To test this hypothesis, we compared de novo germline mutation rates in the hypervariable minisatellite locus, CEB1, in family trios (both parents and their child) of children with leukaemia (n=135) compared with unaffected control families (n=124). The majority of case and control germline mutations were paternal (94%); the mean paternal germline mutation rates of children with leukaemia (0.083) and control children (0.156) were not significantly different (odds ratio, 95% confidence interval: 0.50, 0.23–1.08; P=0.11). There were no significant differences in case and control parental allele sizes, case and control germline mutation progenitor allele sizes (2.74 vs 2.54 kb; P=0.56), case and control mutant allele sizes (2.71 vs 2.67 kb; P=0.90), mutant allele size changes (0.13 vs 0.26 kb; P=0.10), or mutational spectra. Within the limitation of the number of families available for study, we conclude that childhood leukaemia is unlikely to be associated with increased germline minisatellite instability.

Exposure to Medical Test Irradiation and Acute Leukemia Among Children With Down Syndrome: A Report From the Children's Oncology Group

The etiology of acute childhood leukemia is not well understood, particularly among children with Down syndrome, in whom a 10- to 20-fold increased risk of leukemogenesis has been reported compared with children without Down syndrome. We explored the association between medical test irradiation, a postulated leukemogenic agent, and acute leukemia among children with Down syndrome. Children with Down syndrome (controls) were frequency matched on age to children with Down syndrome and leukemia (cases) diagnosed at ages 0 to 19 years during the period 1997-2002 at participating Children's Oncology Group institutions in North America. Telephone interviews were completed with mothers of 158 cases (n = 97 acute lymphoblastic leukemia and n = 61 acute myeloid leukemia) and 173 controls. Paternal interviews were completed with 275 fathers and 40 mothers serving as surrogates. Three irradiation exposure periods were examined: preconception, in utero, and postnatal. Multivariate unconditional logistic regression models were constructed to evaluate the associations of interest, resulting in odds ratios and 95% confidence intervals. There was little evidence that maternal or paternal preconception irradiation exposure, intrauterine exposure, or postnatal exposure contributes to leukemogenesis in children with Down syndrome. Overall, no evidence for an effect of any periconceptional exposure was observed. Similar results were observed among acute lymphoblastic leukemia and acute myeloid leukemia cases analyzed separately. This was the first study, to our knowledge, to examine such an association among this unique patient population. The results do not provide evidence of a positive association between ionizing radiation exposure and acute leukemia among children with Down syndrome. The absence of an association should be encouraging for concerned parents of children with Down syndrome who undergo a series of diagnostic radiographs in the course of their standard care.

Genetic counselling following paternal therapeutic irradiation

We discuss a patient who received adjuvant radiotherapy for stage I seminoma. He was advised to avoid conception for 6 months following treatment. However, his partner became pregnant only shortly after he completed his radiotherapy (i.e. with sperm that had been irradiated). We estimated the dose received by the remaining testis as 30 cGy. Here, we review the information available to advise patients on the risks to the fetus from paternal preconception irradiation. For the population, a doubling dose for hereditary effects of 1 Gy has recently been reaffirmed (United Nations Scientific Committee on the Effects of Atomic Radiation 2001). However, a range of animal studies suggest conception with postmeiotic sperm carries a greater risk of genetic damage than conception with sperm derived from irradiated stem cells. We have attempted to quantify the risks in this particular case. Lead shielding of the testes may reduce radiation received from the primary beam, but internal scatter still produces a risk. In male patients who are potentially fertile, the best advice remains to delay conception after radiotherapy for as long as 6 months. Our case illustrates the need to reinforce such advice.

Comparison of Health and Safety Executive and Cumbrian birth cohort studies of riskof leukaemia/non-Hodgkin’s lymphoma in relation to paternal preconceptionalirradiation

In 1993, a case-control study by the Health and Safety Executive (HSE) assessed the risk ofleukaemia and non-Hodgkin’s lymphoma (LNHL) among children of fathers employed at theSellafield nuclear installation in relation to paternal preconceptional irradiation (PPI). Itconcluded that the statistical association between risk of LNHL and PPI was confined tochildren born in the village of Seascale, where the dose-response was extremely high andvery significant. In contrast, in 2002, a Cumbrian birth cohort study, investigating largelythe same cases, concluded that this statistical association was not significantly differentamong children born inside and outside Seascale and estimated the dose-response insideSeascale to be much lower. This review makes a detailed comparison of the twostudies, considering their design, data and analyses. The differences between theirfindings are due to: (i) differences in the distribution of offspring-years which aredifferential with respect to dose category and Seascale birth status, (ii) a non-Seascalehigh-dose case included in the Cumbrian but not the HSE study, (iii) differencesbetween analyses using categorical and continuous PPI dose and (iv) the presenceof Seascale controls with PPI over 200 mSv in the Cumbrian but not the HSEstudy.

Childhood leukaemia clusters around Sellafield and Dounreay

In 1983, a television programme identified a striking cluster of childhood leukaemia in the coastal village of Seascale, adjacent to the Sellafield nuclear complex in England. Excesses of childhood leukaemia near certain other nuclear installations in Britain were later reported during the 1980s, notably a cluster in west Thurso near Dounreay in Scotland. Detailed radiological investigations. demonstrated that radiation exposures from discharged radioactive material were most unlikely to he the cause of these excesses and no serious deficiencies in these assessments have been discovered despite exhaustive searches. In 1990. a report was published suggesting that occupational radiation exposure of men before the conception of their children could be responsible for the Seascale cluster. Extensive research has not suppored a causal link between paternal preconceptional radiation dose and childhood leukaemia, and the idea that radiation exposure of fathers materially increases the risk of leukaemia, in offspring and could account for the clusters has now effectively been abandoned. In contrast, evidence has mounted that childhood leukaemia has an infectious basis and that unusual population mixing increases the risk of the disease. It now seems that population mixing is the explanation for the excesses of childhood leukaemia near nuclear sites and at other locations with no enhanced exposure to radiation.

Leukaemia and non-Hodgkin's lymphoma in children of male Sellafield radiation workers.

Our objective was to investigate if there was (i) an excess risk of leukaemia/non-Hodgkin's lymphoma among children of male radiation workers at the Sellafield nuclear installation in Cumbria, northwest England; (ii) a dose-response relationship between fathers' preconceptional irradiation and their children's risk of leukaemia/non-Hodgkin's lymphoma; and (iii) whether any observed association could be explained by demographic factors. We performed a cohort study of live births, 1950-1991 in Cumbria, followed up to age 25 years or the end of 1991, comparing the risk of leukaemia/non-Hodgkin's lymphoma among all 9,859 children of male radiation workers to that among all 256,851 children of non-Sellafield fathers. Children of radiation workers had a higher risk of leukaemia/non-Hodgkin's lymphoma than other children [rate ratio (RR) = 1.9, 95% confidence interval (CI) 1.0-3.1, p = 0.05]. Adjustment for population mixing greatly reduced the excess risk in the village of Seascale, adjacent to Sellafield, but had little effect elsewhere. The risk increased significantly with father's total preconceptional external radiation dose (RR(100mSv) = 1.6, 95% CI 1.0-2.2, p = 0.05). This dose-response was not reduced by adjustment for population mixing. Although our 13 exposed cases included 10 considered previously (Gardner et al., BMJ 1990;300:423-34), we used a cohort rather than a case-control design, with wider temporal and geographic boundaries, and confirmed the statistical association between father's preconceptional irradiation and child's risk of leukaemia/non-Hodgkin's lymphoma that they reported. The possibility remains that paternal preconceptional irradiation may be a risk factor for leukaemia/non-Hodgkin's lymphoma, and this effect may not be confined to Seascale.

Induction of stem cell cycling in mice increases their sensitivity to a chemical leukaemogen: implications for inherited genomic instability and the bystander effect

Preconception paternal irradiation (PPI) modifies haemopoietic and stromal tissues of offspring and increases risk of generating lympho-haemopopietic malignancy if those offspring are then exposed to a leukaemogen. We hypothesised that this increased risk was related to inherited damage which had caused increased stem cell proliferation rates. To test for this link, in vivo, rapid stem cell proliferation was established by giving sub-lethal irradiation (3 Gy γ-rays) and allowing 3 days recovery. At this stage, 60% of haemopoietic spleen colony-forming units (CFU-S) were in DNA-synthesis, compared to <10% in unirradiated controls. Two groups of mice, unirradiated controls and irradiated animals, were then injected with 50 mg/kg methyl nitrosourea (MNU) and observed daily for onset of lympho-haemopoietic malignancy. In a further control group of 60 mice, irradiated but not injected with MNU, only one leukaemia developed. In unirradiated controls, 20% of the mice developed malignancies between 3 and 8 months later: in the irradiated, MNU-treated groups, 95% developed malignancies between 2 and 7 months later. Thus, at least one powerful potentiating mechanism for induction of lympho-haemopoietc malignancy following inherited damage can be related to haemopoietic stem cell proliferation. Genomic instability is exposed by cell proliferation and has been implicated in this type of damage. However, a regulatory stromal microenvironment plays a part in inducing that proliferation. Thus, the microenvironment is the effective “bystander” which is thought to promote and amplify genomic instability, and thereby influence the induction of malignancy both in PPI offspring and in mice with induced stem cell proliferation.

Paternal preconceptional irradiation, population mixing and solid tumors in the children of radiation workers (England).

To investigate whether there was an increased incidence of solid tumors among offspring of male radiation workers at the Sellafield nuclear installation in Cumbria, northwest England and whether paternal preconceptional irradiation was associated with the risk of solid tumors. A cohort study of 266,710 live births in Cumbria, 1950-1991, followed up to age 25 years on the end of 1991. Children of radiation workers had a non-significantly increased risk of solid tumors (RR= 1.5, 95% CI: 0.9-2.4, p = 0.09), determined largely by an increased risk of cancers excluding leukemias, lymphomas, brain, spinal and gender-specific tumors (RR= 1.9, 95% CI: 1.0-3.3, p = 0.05), which was partly explained by differing patterns of parental migration (adjusted RR= 1.7, 95% Cl: 0.8-3.2, p = 0.50). Within children of radiation workers there was no evidence of an increased risk with increasing paternal preconception dose of external radiation (hazard ratio per 100 mSv for all solid tumors=0.6, 95% CI: 0.1-1.8, p = 0.52). Any observed excess of solid tumors in children of radiation workers may be partly explained by population mixing. Fathers' occupational exposure to radiation before conception was not found to be risk factor for solid tumors in their children.

Transgenerational effects of preconception paternal contamination with (55)Fe.

The conjecture that germline mutations induced by radiation exposure before conception may predispose subsequent offspring to cancer remains contentious. Previous experimental studies have shown that preconception paternal irradiation with (239)Pu induces perturbations in the hemopoietic systems of offspring and influences sensitivity to a secondary carcinogen. In the present study, male DBA2 mice were injected intravenously with the Auger electron emitter (55)Fe (4 kBq g(-1)) 18 or 84 days before mating with normal females. Comet analysis showed an increased incidence of DNA strand breaks in sperm from contaminated animals after 84 days, but not after 18 days, indicating spermatogonial rather than spermatid damage. Offspring were either assayed for changes in bone marrow stem cells and committed progenitors or challenged with the chemical carcinogen methyl nitrosourea (MNU, 50 mg/kg) at 10 weeks of age and monitored for the onset of malignancy. Offspring from irradiated fathers had normal peripheral blood profiles, although the stem cell population was amplified in offspring arising from those exposed to (55)Fe at 84 days before conception. Exposure to MNU significantly increased the incidence of lympho-hemopoietic malignancies in offspring from the 84-day group, but not in those from the 18-day group. These findings support the hypothesis that aberrations that are potentially leukemogenic may be transmitted to offspring after radiation damage to the paternal germline.

Risk of stillbirth in offspring of men exposed to ionising radiation

Radiation genetic risk models are employed to predict the frequency ofradiation-related stillbirths to partners of occupationally exposed maleworkers, using the incidence data recently reported by Parker et al from an epidemiological study of Cumbrian births. Expanding on previouslydeveloped conservative risk estimates suggests that, of the 130 observedstillbirths to partners of male radiation workers, 0.3 cases would beattributable to paternal preconceptional irradiation, in contrast to the 17.5(95% confidence interval: 3.1 to 31.9) cases predicted by Parker et al from their preferred dose-response model. The incompatibility of the resultsreported by Parker et al with those from other investigations, bothepidemiological and experimental, and the inability of the study to consider anumber of factors which might affect stillbirth rates, particularly thoserelating to the mother, make it difficult to accept that paternal irradiationreceived occupationally could have contributed to a detectable increase instillbirths.

Scientific Uncertainty: An Insuperable Obstacle to Compensation for Environmental Causes of Ill Health?

In this paper, I review the conceptual and legal obstacles faced by those who seek redress for health detriment which is though to be environmental in origin. I use two case studies concerned with radiation: one is related to energy production (paternal pre-conceptional irradiation of workers at a nuclear fuel reprocessing plant), the other involves electricity distribution (the alleged link between leukaemia and power cables). Judicial approaches to scientific uncertainty inherent in these two cases are examined. The more science points to a hitherto unimagined range of threats to human health, the fewer grounds remain for confidence in the capacity of tort to secure appropriate compensation for the putative victims.

Hemopoietic Damage and Induction of Leukemia in Offspring due to Preconception Paternal Irradiation from Incorporated Plutonium-239

Preconception paternal irradiation has been implicated in a localized excess of childhood leukemia and non-Hodgkin's lymphoma close to a nuclear reprocessing plant. Other epidemiological studies, however, threw doubt on the validity of this hypothesis. Experimental evidence implicating preconception paternal X rays in the development of lung and skin cancers has also been questioned. In this study, (239)Pu (0, 128 or 256 kBq kg(-1)) was injected into male CBA-H and DBA-2 mice 12 weeks before they were mated with CBA-H and C57BL/6 females. Their offspring were assessed for hematological status at 6 to 18 weeks of age or were treated with either 3.3 Gy whole-body gamma rays or methylnitrosourea (MNU, 50 mg kg(-1)) and monitored for onset of malignancies of the lymphoid and hemopoietic system. As a group, offspring were normal hematologically, but up to 35% of individual mice had femoral cellularities and numbers of spleen and fibroblastoid colony-forming cells outside the normal range. Exposure of the offspring to radiation or MNU significantly increased the rate of incidence of lymphoid and myeloid leukemias. Simulation of the experiments with preconception gamma irradiation indicated that damage to the spermatogenic stem cell was an important factor. It is concluded that preconception paternal irradiation can influence susceptibility of offspring to a subsequent exposure to a carcinogen.

A comparison of the risk of stillbirth associated with paternal pre-conception irradiation in the Sellafield workforce with that of stillbirth and untoward pregnancy outcome among Japanese atomic bomb survivors

A comparison is made of the relative risks associated with paternal pre-conception irradiation of stillbirth and untoward pregnancy outcome (stillbirths, congenital malformations, neonatal deaths) in the offspring of the Japanese atomic bomb survivors and of stillbirth in the offspring of Sellafield workers. It is concluded that the pre-conception exposure risks of stillbirth in the offspring of Sellafield workers are statistically incompatible with the Japanese data at the 5% level. Other human and experimental data relating to the induction of congenital abnormalities are briefly reviewed.

Stillbirths among offspring of male radiation workers at Sellafield nuclear reprocessing plant

Ionising radiation is a known mutagen, but few studies have examined transgenerational effects of paternal exposure in human beings. The workforce at the Sellafield nuclear reprocessing plant in the county of Cumbria, UK, is the most highly exposed workforce in western Europe and North America. This study, which is part of a larger programme of work investigating the health of the children of the Sellafield workforce, set out to find whether there was evidence of an association between stillbirth risk and paternal exposure to ionising radiation. We collected details from birth registration documents for all singleton 248,097 livebirths and 3715 stillbirths in the county of Cumbria 1950-89. Within this cohort the 130 stillbirths and 9078 livebirths to partners of male radiation workers employed at Sellafield were identified. Logistic regression was used to analyse the relation between stillbirth risk and father's preconceptional radiation exposure, with adjustment for social class, year of birth, father's age, and birth order. A significant positive association was found between the risk of a baby being stillborn and the father's total exposure to external ionising radiation before conception (adjusted odds ratio per 100 mSv 1.24 [95% CI 1.04-1.45], p=0.009). The risk was higher for stillbirths with congenital anomaly and was highest for the nine stillbirths with neural-tube defects. The statistical models predicted that, were the association to be interpreted as causal, between 0 and 31.9 of the 130 stillbirths to the workforce may be attributable to father's radiation exposure. The findings of an increased risk of stillbirth with increasing paternal occupational exposure to external radiation are qualitatively consistent with those from animal models, though the risk estimate is higher. Although we cannot exclude the possibility of an unmeasured risk factor for stillbirth, confounded with paternal preconceptional irradiation, extensive checks confirmed that the statistical models were a good fit to the data and there was not statistical evidence of unmeasured factors.

Stillbirth and paternal preconceptional radiation exposure

The hypothesis that a father's exposure to radiation increases the risk of leukaemia in children subsequently conceived was suggested in 1990 by Gardner and colleagues.1 The proposal gave rise to intense publicity, much concern among workers in the nuclear industry, and expensive litigation. Further studies have given at most weak support to this hypothesis, and some scientists have dismissed it entirely.2 Others have noted that heritable effects are more likely to manifest themselves as congenital anomalies than as leukaemia,3 and no excess of these anomalies near Sellafield (the nuclear establishment in Cumbria, UK, around which Gardner's study1 on leukaemia was conducted) has been found.

Transgenerational susceptibility to leukaemia induction resulting from preconception, paternal irradiation

The clustered excess of childhood leukaemia and non-Hodgkin's lymphoma at Seascale, close to the nuclear reprocessing plant at Sellafield in the UK is well authenticated and has remained a 'current topic' for over a decade. Its root cause has not been established. Following a study suggesting that parental irradiation exposure prior to conception was a factor, a recent laboratory based report reopened the debate by indicating the potential for preconception, paternal irradiation (PPI) to result in increased or accelerated induction of lympho-myeloid malignancy in offspring subjected to a recognized leukaemogen. This short commentary presents those new findings in the light of the many and diverse epidemiological investigations of first generation malignancies following parental exposure, the majority of which indicate no real evidence to support the concept that patterns of lympho-myeloid malignancy reflect levels of PPI. Other experimental work supporting PPI are considered against unsuccessful attempts to reproduce them. The alternative, and more popular, hypothesis of infection spread via population mixing, which is more ubiquitous than confinement to nuclear localities, is introduced. Mechanisms of potentiation by PPI are considered, though the danger of applying these current findings to explain the enigma of Seascale, or any other cluster, is recognized.

Induction of lympho-haemopoietic malignancy: impact of preconception paternal irradiation

Purpose: To investigate the effects of preconception paternal irradiation (PPI) from injected 239Pu on the susceptibility to induction of lympho-haemopoietic malignancy by subsequent irradiation or exposure to a chemical carcinogen. Materials and Methods: The male CBA/H and DBA2 mouse was injected with 0, 128 or 256Bqg -1 239Pu 12 weeks before mating with the normal CBA/H and C57Bl female respectively. CBA/H offspring were exposed to 3.3Gy gamma -rays total body irradiation: BDF offspring were injected with 50mgkg -1methyl nitrosourea (MN1 U). The offspring were assayed for changes in bone marrow progenitor cell numbers and chromosome aberrations and were followed up for subsequent induction of neoplasia. Results: While the untreated mouse showed a normal distribution for cellularity, spleen colony-forming units (CFU-S) and fibroblastoid colony-forming units (CFU-F), significant numbers of PPI offspring presented levels outside the normal range. There was a tendency for them also to show increased, dose-related, levels of chromosomal aberrations. Offspring treated with irradiation or MNU developed an increased incidence of lymphohaemopoietic malignancies. Conclusions: These studies have shown that PPI results in offspring that are more susceptible to the induction of lymphohaemopoietic malignancy on encountering a secondary carcinogenic insult. This may be linked to inherited chromosomal instability and abnormal kinetics of haemopoiesis. The experiments indicate a potential mechanism by which an increased incidence of leukaemia may be linked to PPI.

Cancer in the offspring of radiation workers: a record linkage study

Objectives: To test the “Gardner hypothesis” that childhood leukaemia and non-Hodgkin lymphoma can be caused by fathers' exposure to ionising radiation before the conception of the child, and, more generally,...