Ionising radiation and genetic risks. XVI. A genome-based framework for risk estimation in the light of recent advances in genome research

Sankaranarayanan, K.; Nikjoo, Hooshang

doi:10.3109/09553002.2010.518214

Cited by 19 publications

(18 citation statements)

References 123 publications

(108 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Russell and used for 40 years required heroic efforts and >100,000 animals per study. However, recent technical developments, especially next-generation DNA sequencing and advanced computational techniques, have catapulted the field of germ-cell mutagenesis beyond its traditional limitations and into the realm of the possible [Sankaranarayanan and Nikjoo, 2011].…”

Section: Technical Developments and Recent Discoveries Of De Novo Germentioning

confidence: 99%

“…Indeed, many people have considered and anticipated such a possibility [Wyrobek et al, 2007;Sankaranarayanan and Nikjoo, 2011;Yauk et al, 2012]. The technical breakthrough represented by next-generation sequencing, especially third-generation sequencing, which will permit characterization of large stretches of repeated sequences, coupled with epigenomic analyses, will dispel our sense of complacency regarding germ-cell mutagens in our environment.…”

Section: Need For a Declaration Panel And Implications Of Declaring Amentioning

confidence: 99%

“…Despite the negative epidemiology studies [Winther et al, 2012], I think it unlikely that cancer chemotherapeutic agents are not germ-cell mutagens in humans. Genomic technologies should provide more definitive insight into this conundrum [Sankaranarayanan and Nikjoo, 2011; C.L. Yauk et al, in preparation].…”

Section: Possible Human Germ-cell Mutagensmentioning

confidence: 99%

See 2 more Smart Citations

Declaring the existence of human germ‐cell mutagens

DeMarini

2012

Environ and Mol Mutagen

View full text Add to dashboard Cite

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.

show abstract

Section: Technical Developments and Recent Discoveries Of De Novo Germentioning

confidence: 99%

Section: Need For a Declaration Panel And Implications Of Declaring Amentioning

confidence: 99%

See 1 more Smart Citation

Declaring the existence of human germ‐cell mutagens

DeMarini

2012

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

“…For over two decades, Sankaranarayanan (Sankaranarayanan and Wassom 2008;Sankaranarayanan and Nikjoo 2011) advanced several model concepts that could be used to develop or modify a way to assess human genetic risk from exposure to ionizing radiation. The existing paradigm is based on the assumption that adverse effects of radiation will be manifested in progeny of exposed individuals as genetic diseases similarly distributed as those that occur naturally in the population.…”

Section: Detecting Germ Cell Mutagenesis In Offspring-theorymentioning

confidence: 99%

Preconception exposure to mutagens: medical and other exposures to radiation and chemicals

Mulvihill

2012

J Community Genet

View full text Add to dashboard Cite

Contrary to intuition, no environmental exposure has been proved to cause human germ line mutations that manifest as heritable disease in the offspring, not among the children born to survivors of the American atomic bombs in Japan nor in survivors of cancer in childhood, adolescence, or young adulthood who receive intensive chemotherapy, radiotherapy, or both. Even the smallest of recent case series had sufficient statistical power to exclude, with the usual assumptions, an increase as small as 20 % over baseline rates. One positive epidemiologic study of a localized epidemic of Down syndrome in Hungary found an association with periconceptual exposure to a pesticide used in fish farming, trichlorfon. Current population and occupational guidelines to protect against genetic effects of ionizing radiation should continue, with the understanding they are based on extrapolations from mouse experiments and mostly on males. Presently, pre-conceptual counseling for possible germ cell mutation due to the environment can be very reassuring, at least based on, in a sense, the worst-case exposures of cancer survivors. Prudence demands further study. Future work will address the issue with total genomic sequencing and epigenomic analysis.

show abstract

“…Ideally, it is calculated by dividing the average spontaneous mutation rate of a set of genes by the average induced rate for the same set of genes, although this has not always been possible. 1 The quantity [1/DD] is called the relative mutation risk (RMR) per unit dose. The DD estimate in current use for low dose, chronic, low LET irradiation (the radiation conditions used for risk estimation) is 1 Gy.…”

Section: The Doubling Dose (Dd) Methods Of Risk Estimationmentioning

confidence: 99%