Mutant Frequency of Radiotherapy Technicians Appears to Be Associated With Recent Dose of Ionizing Radiation

Messing, Karen; Ferraris, Jocelyne; Bradley, W. E. C.; Swartz, Joel D.; Seifert, Ana María

doi:10.1097/00004032-198910000-00003

Cited by 42 publications

(10 citation statements)

References 14 publications

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“…In radiotherapy patients (breast cancer), Messing et a1. (88) observed after much higher doses (4 Gy) mutation frequencies of only 1 percent of those at the very low doses and dose rates, suggesting that mutation induction in human cells in vivo might follow a supralinear dose response, as observed by Waldren et al(85) in tissue culture. At higher doses, multiple instances of damage and cell killing became prominent, reducing the mutation yield.…”

Section: Mutation Frequency In Peripheral T-lymphocytes From Occupatimentioning

confidence: 58%

“…Messing et al (88) investigated whether mutant frequency in peripheral T-lymphocytes of radiotherapy technicians exposed, on average, to 0.3 cGy per month of cobalt-60 gamma radiation can be associated with recently absorbed dose. The study cohort consisted of 13 exposed technicians wearing dosimeters.…”

Section: Mutation Frequency In Peripheral T-lymphocytes From Occupatimentioning

confidence: 99%

See 1 more Smart Citation

Consistencies and Discrepancies: Current Perspectives on Low Dose Health Effects of Ionizing Radiation

Nussbaum

Köhnlein

1996

Applied Occupational and Environmental Hygiene

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Section: Mutation Frequency In Peripheral T-lymphocytes From Occupatimentioning

confidence: 58%

Section: Mutation Frequency In Peripheral T-lymphocytes From Occupatimentioning

confidence: 99%

Consistencies and Discrepancies: Current Perspectives on Low Dose Health Effects of Ionizing Radiation

Nussbaum

Köhnlein

1996

Applied Occupational and Environmental Hygiene

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“…Investigations include exposures to ionizing radiation, such as the survivors of the bombing of Hiroshima (Langlois et al, 1987(Langlois et al, , 1993Hakoda et al, 1988), accidents such as Chernobyl Livingston et al, 1997) and Goiania (Straume et al, 1991) and other medical (Nicklas et al, 1990;Grant and Bigbee, 1994), environmental GRANT (Bridges et al, 1991) and occupational studies (Messing et al, 1989;Straume et al, 1992).…”

Section: Somatic Mutational Analysismentioning

confidence: 99%

Elevated Levels of Somatic Mutation as a Biomarker of Environmental Effects Contributing to Breast Carcinogenesis

Grant¹

2002

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and AUTHOR(S)Stephen G. Grant, Ph.D. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)8 ABSTRACT (Maximum 200 Words)Risk factors for the development of breast cancer remain largely unknown, especially those associated with the effect of the environment. Despite the known influence of hormonal factors, breast tumorigenesis has been shown to involve an accumulation of serial genetic changes in cancer genes. X-irradiation is a genotoxic exposure that has been identified as a risk factor for breast cancer. If somatic mutation is a major mechanism that drives the process of breast carcinogenesis, we hypothesize that breast cancer should develop preferentially in women with higher frequencies of somatic variation, as measured at a neutral reporter locus. The rate of somatic mutation is determined by exposure to endogenous and exogenous genotoxic agents and by an individual's ability to deal with such exposures through biotransformation of xenobiotics and DNA repair. We are using two established bioassays of in vivo human somatic mutation to study a large population of newly diagnosed primary breast cancer patients. These genetic/environmental interactions can be quantitated simply from observed effect, before we have completely understood the underlying mechanisms. Our primary goal is to provide a rationale for simple laboratory blood tests to be incorporated into the risk estimation equation for breast cancer.14. 3 IntroductionBreast cancer is one of the most common malignancies in the western world, and increases in incidence are being seen worldwide. Risk factors for the development of breast cancer remain largely unknown, with up to 75% of breast cancers occurring in the absence of established risk factors. The three risk factors that have been established are: family history of breast cancer, metabolic factors related to hormone production, and exposure to X-irradiation (Gail and Benichou, 1992;Claus et al., 1994). This study proposes that the last mentioned factor, exposure to ionizing radiation, is actually indicative of a larger involvement of genotoxicity in the etiology of breast cancer. This suggests that exposure to carcinogenic chemicals and susceptibility to mutagenesis and carcinogenesis play a significant role in determining who will develop a tumor of the breast. Indeed, evidence is mounting that the two known breast cancer susceptibility genes, BRCA1 and BRCA2 are actually DNA repair genes that modulate the genotoxi...

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“…Factors that affect the frequency and molecular nature of somatic mutation in people have been extensively explored using the lymphocyte-based assays. These factors include age; life-style exposures such as smoking and diet; occupational, therapeutic, environmental, and accidental exposures; and inherited susceptibilities [for examples, see Trainor et al, 1984;Messing and Bradley 1985;Hakoda et al, 1988;Messing et al, 1989;Bigbee et al, 1990;McGinniss et al, 1990;Kelsey et al, 1991;Jones et al, 1993Jones et al, , 1995Jones et al, , 2002Cole and Skopek 1994;Akiyama et al, 1995Akiyama et al, , 1996Duthie et al, 1995;Hirai et al, 1995;Lambert et al, 1995;da Cruz et al, 1996;Kyoizumi et al, 1996;Moore et al, 1997;Hou et al, 2001;Nyberg et al, 2003;Rice et al, 2004].…”

Section: Introductionmentioning

confidence: 99%

Studies of thioguanine‐resistant lymphocytes induced by in vivo irradiation of mice

Jones

Burkhart-Schultz

Strout

et al. 2008

Environ and Mol Mutagen

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The frequency of Hprt-deficient lymphocytes in mice after in vivo gamma irradiation, has been found to vary as a function of time elapsed after exposure and irradiation dose. The frequency of mutant lymphocytes in spleen was determined using an in vitro, clonogenic assay for thioguanine-resistant T-lymphocytes. Mice were exposed to single doses of 0-400 cGy from cesium-137 or to eight daily doses of 50 cGy. The time to maximum-induced mutant frequency was 3 weeks. The dose response was strikingly curvilinear at 3-5 weeks after irradiation, but less precisely defined for 10-53 weeks after exposure, being fit by either linear or quadratic dependence. Three weeks after eight daily 50 cGy exposures, mutant frequency was elevated above controls and mice exposed to 50 cGy (which were not distinct from the nonirradiated controls), but only 17% in that of mice given a single 400 cGy fraction. This fractionation effect and the curvilinearity of the early dose-response curve suggested that saturation of repair increased the yield of mutations at higher acute doses. The decline of spleen mutant frequency in mice observed between 5 and 10 weeks after irradiation may reflect selection against some mutants. The marked variation of mutant frequency, as a function of time after irradiation and of dose rate, emphasize the need to evaluate these variables carefully and consistently in future studies.

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Mutant Frequency of Radiotherapy Technicians Appears to Be Associated With Recent Dose of Ionizing Radiation

Cited by 42 publications

References 14 publications

Consistencies and Discrepancies: Current Perspectives on Low Dose Health Effects of Ionizing Radiation

Consistencies and Discrepancies: Current Perspectives on Low Dose Health Effects of Ionizing Radiation

Elevated Levels of Somatic Mutation as a Biomarker of Environmental Effects Contributing to Breast Carcinogenesis

Studies of thioguanine‐resistant lymphocytes induced by in vivo irradiation of mice

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