Prevalence of Adult-Onset Multifactorial Disease among Offspring of Atomic Bomb Survivors

Fujiwara, Saeko; Suyama, Akihiko; Cologne, John; Akahoshi, Masazumi; Yamada, Michiko; Suzuki, Gen; Koyama, Kazuaki; Takahashi, Norio; Kasagi, Fumiyoshi; Grant, EJ; Lagarde, Emmanuel; Hsu, Wan-Ling; Furukawa, Kyoji; Ohishi, Waka; Tatsukawa, Yoshimi; Neriishi, Kazuo; Takahashi, Ikuno; Ashizawa, Kei; Hida, Ayumi; Imaizumi, M.; Nagano, Jun; Cullings, Harry M.; Katayama, Hiroaki; Ross, N. P.; Kodama, Kazunori; Shore, Roy E.

doi:10.1667/rr1392.1

Cited by 25 publications

(21 citation statements)

References 19 publications

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“…Other analyses revealed few indications of excess risk for all malignant endpoints, whether for mortality or morbidity, and all other mortality endpoints [105–110] (Table 2). There were no indications of radiation-associated increases in adult-onset multifactorial disease [111, 112] (Table 2). …”

Section: Epidemiological Evidence For Transgenerational Health Effmentioning

confidence: 99%

Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents

Little

Goodhead

Bridges

et al. 2013

Mutation Research/Reviews in Mutation Research

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In this article we review health effects in offspring of human populations exposed as a result of radiotherapy and some groups exposed to chemotherapy. We also assess risks in offspring of other radiation-exposed groups, in particular those of the Japanese atomic bomb survivors and occupationally and environmentally exposed groups. Experimental findings are also briefly surveyed. Animal and cellular studies tend to suggest that the irradiation of males, at least at high doses (mostly 1 Gy and above), can lead to observable effects (including both genetic and epigenetic) in the somatic cells of their offspring over several generations that are not attributable to the inheritance of a simple mutation through the parental germ line. However, studies of disease in the offspring of irradiated humans have not identified any effects on health. The available evidence therefore suggests that human health has not been significantly affected by transgenerational effects of radiation. It is possible that transgenerational effects are restricted to relatively short times post-exposure and in humans conception at short times after exposure is likely to be rare. Further research that may help resolve the apparent discrepancies between cellular/animal studies and studies of human health are outlined.

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Section: Epidemiological Evidence For Transgenerational Health Effmentioning

confidence: 99%

Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents

Little

Goodhead

Bridges

et al. 2013

Mutation Research/Reviews in Mutation Research

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“…All but three of these studies found no evidence of human germ-cell mutagens, including the decades-long evaluation of the survivors of the atomic bomb explosions at Hiroshima and Nagasaki in 1945 [Schull et al, 1981;Kodaira et al, 1995;Fujiwara et al, 2008].…”

Section: Why Have No Human Germ-cell Mutagens Been Identified?mentioning

confidence: 99%

“…Approximately a dozen epidemiological studies have been conducted since the 1950s to investigate whether ionizing radiation, chemotherapy, or pesticides might be human germ-cell mutagens [reviewed by Shelby, 1994;Dubrova, 2003;Wyrobek et al, 2007;Winther et al, 2012]. All but three of these studies found no evidence of human germ-cell mutagens, including the decades-long evaluation of the survivors of the atomic bomb explosions at Hiroshima and Nagasaki in 1945 [Schull et al, 1981;Kodaira et al, 1995;Fujiwara et al, 2008].…”

Section: Why Have No Human Germ-cell Mutagens Been Identified?mentioning

confidence: 99%

Declaring the existence of human germ‐cell mutagens

DeMarini

2012

Environ and Mol Mutagen

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After more than 80 years of searching for human germ‐cell mutagens, I think that sufficient evidence already exists for a number of agents to be so considered, and definitive confirmation seems imminent due to the application of recently developed genomic techniques. In preparation for this, an assessment panel of internationally recognized experts in germ‐cell biology and genomics is required to consider either the current evidence now, or impending genomic evidence later, to declare whether an agent is a human germ‐cell mutagen. I propose that such a panel be organized under the aegis of the World Health Organization and constructed similarly to the working groups assembled by the International Agency for Research on Cancer for the evaluation of human carcinogens. Support from prominent national and international organizations would be important. Many regulatory agencies already have procedures in place for assessing potential human germ‐cell mutagens, and the time is approaching when definitive genomic data in humans will obligate such evaluations. In my view, application of an IARC‐type of assessment using available evidence leads to the conclusion that ionizing radiation, cancer chemotherapy, cigarette smoking, and air pollution are “Group 1” human germ‐cell mutagens. Consideration of the potential adverse health effects to the unexposed offspring of an exposed parent will usher in an entirely new realm of environmental health assessment. I suggest that the long search for human germ‐cell mutagens is about to end, and a demonstration of the much‐anticipated linkage between heritable disease and environmental factors is poised to begin. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.

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“…A large number of the studies of children of fathers exposed to environmental mutagens have failed to reveal evidence of a significantly increased risk of cancer or genetic disease. The most recently published studies have shown no increased risk of adult-onset multifactorial disease in children of atomic bomb survivors and no increased risk of cancer among children of cancer chemotherapy patients [Fujiwara et al, 2008;Madanat-Harjuoja et al, 2010]. However, there have been studies that have found paternal pre-conceptional chemical exposure has been associated with a slightly increased risk of childhood cancers [Cordier et al, 1997;Ji et al, 1997;Cordier et al, 2004].…”

Section: Lack Of De¢nitive Evidence Of Human Germline Mutagensmentioning

confidence: 99%

Germ cell mutagens: Risk assessment challenges in the 21st century

Singer

Yauk

2010

Environ and Mol Mutagen

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Heritable mutations may result in a wide variety of detrimental outcomes, from embryonic lethality to genetic disease in the offspring. Despite this, today's commonly used test batteries do not include assays for germ cell mutation. Current challenges include a lack of practical assays and concrete evidence for human germline mutagens, and large data gaps that often impede risk assessment. Moreover, most regulatory assessments are based on the assumption that somatic cell mutation assays also protect the germline by default, which has not been adequately confirmed. The field is also faced with new challenges aimed at dramatically reducing animal testing, and attempts to rapidly classify thousands of chemicals using high throughput in vitro assays. These approaches may not adequately capture effects that may be particular to gametes, since many aspects of the germline are unique. In light of these challenges, an urgent need exists to develop new approaches to evaluate the potential of toxicants to cause germline mutation. The application of new technologies will greatly enhance our understanding of mutation in humans exposed to environmental mutagens. However, we must be poised to collect and interpret these data, and facilitate risk translation to regulators and the public. Genetic toxicologists must also become actively involved in the development of high-throughput tools to study germline mutation. Appropriate attention to these areas will result in the development of policies that prioritize the protection of the germline and future generations from DNA sequence mutations.

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Prevalence of Adult-Onset Multifactorial Disease among Offspring of Atomic Bomb Survivors

Cited by 25 publications

References 19 publications

Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents

Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents

Declaring the existence of human germ‐cell mutagens

Germ cell mutagens: Risk assessment challenges in the 21st century

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