In vivo mutagenesis in the cynomolgus monkey: Time course ofHPRT mutant frequency at long time points following ethylnitrosourea exposure

Zimmer, David M.; Aaron, C.S.

doi:10.1002/(sici)1098-2280(1997)29:2<117::aid-em2>3.0.co;2-b

Cited by 10 publications

(6 citation statements)

References 17 publications

(3 reference statements)

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“…Importantly, the animals used in this study had been the subject of a separate toxicology study, and thus had unexpected characteristics which complicated our analysis. For example, animal 7008 had a mean spontaneous MF of 16.4 ϫ 10 -6 , much higher than the historical spontaneous MF in our studies (mean MF Ϯ SD ϭ 2.9 Ϯ 2.9 ϫ 10 -6 based on 131 determinations in 33 animals [Zimmer and Aaron, 1997]). It was ultimately determined that the high MF in this animal was due to a proliferating prethymic mutant clone [Mattano et al, 1995].…”

Section: Adozelesincontrasting

confidence: 61%

“…By week 25, when CE had returned to pretreatment values, the MF was 3.6 ϫ 10 -6 , not different from the mean pretreatment MF of 2.6 ϫ 10 -6 for this animal. In our experience with ENU [Zimmer et al, 1991;Zimmer and Aaron, 1997], a positive mutagen in this assay, elevation of MF was relatively persistent, with onset occurring only after about 8 weeks. This characteristic delay in onset (in contrast to our results with CP) could be attributed to stem cell kinetics.…”

Section: Cyclophosphamidementioning

confidence: 67%

“…In the present study, we report hprt mutant frequencies following in vivo treatment with a series of known genotoxins: ethylmethane sulfonate (EMS), chloroethylmethane sulfonate Cl-EMS), cyclophosphamide (CP), adozelesin, and CC-1065; the latter two are Pharmacia & Upjohn antitumor agents known to bind in the minor groove of DNA with strong specificity for ATT sites [Weiland and Dooley, 1991]. Results with ethylnitrosurea (ENU) in this system have been previously reported [Zimmer et al, 1991;Zimmer and Aaron, 1997].…”

Section: Introductionmentioning

confidence: 73%

“…The utility of the hprt locus for monitoring somatic cell mutation rates and frequencies in peripheral blood T-lymphocytes by measuring resistance to 6-TG has been extensively documented. Species in which clonal hprt mutant frequencies have been studied in vivo include mice [Jones et al, 1987;Dempsey and Morley, 1986;Zimmer and Aaron, 1987], rats [Aidoo et al, 1991;vanDam et al, 1992], cynomolgus monkeys [Zimmer et al, 1991;Zimmer and Aaron, 1997], and humans [reviewed by Cariello and Skopek, 1993;Cole and Skopek, 1994].…”

Section: Introductionmentioning

confidence: 99%

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Lack of response to multiple genotoxic agents at the hprt locus in peripheral blood T‐lymphocytes of cynomolgus monkeys

Zimmer¹,

Harbach²,

Mattano³

et al. 1999

Environ. Mol. Mutagen.

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We tested the ability of a series of known genotoxic agents to cause mutations at the hprt locus in peripheral blood T-lymphocytes of cynomolgus monkeys as measured by the ability to form clones in the presence of 6-thioguanine. Ethylmethane sulfonate (EMS, 300 mg/kg i.p.), chloroethylmethane sulfonate (CI-EMS, 35 or 50 mg/kg i.p.), and the Pharmacia & Upjohn antitumor agents adozelesin (1.6, 4, 6, or 8 microg/kg i.v.) and CC-1065 (6 microg/kg i.v.) were all negative in the hprt mutation test. Results with cyclophosphamide (CP, 75 mg/kg i.v.) were equivocal. Adozelesin, CC-1065, and CI-EMS treatments increased the percentage of T-lymphocytes with chromosome aberrations, as well as inducing types of aberrations not seen in control cells. EMS and CP were not tested for chromosome aberrations. We have previously shown that treatment of monkeys with 77 mg/kg ENU substantially increased the hprt mutant frequency, with a lag time of approximately 77 days between treatment and peak MF values. The results of the present study suggest a low sensitivity of the hprt mutation assay to certain classes of genotoxic agents in cynomolgus monkeys.

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Section: Adozelesincontrasting

confidence: 61%

Section: Cyclophosphamidementioning

confidence: 67%

Section: Introductionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lack of response to multiple genotoxic agents at the hprt locus in peripheral blood T‐lymphocytes of cynomolgus monkeys

Zimmer¹,

Harbach²,

Mattano³

et al. 1999

Environ. Mol. Mutagen.

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“…A large number of researches show that human peripheral blood lymphocytes hypoxantine-guanine phpsphoribosyl transferase (HPRT) gene, which is a chemical and ionizing radiation sensitive mutagen loci (Nicklas et al, 1991;Zimmer et al, 1997;Hamdan et al, 1999;Helleday et al, 2000), was closely related to the p53 and bcl-2 gene (Liu et al, 1997;Phillips, Gebow et al, 1997), which had been demonstrated strongly association with cancer development (Murray et al, 2012;Zeestraten et al, 2013),especially with breast cancer and esophageal cancer (Bellini et al, 2012;Walerych et al, 2012). Therefore, it is worthy to emphasize that the occupational X-ray radiation exposure might interact with phosphoribosyl gene mutation contribute to cancer susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Nested Case-control Study of Occupational Radiation Exposure and Breast and Esophagus Cancer Risk among Medical Diagnostic X Ray Workers in Jiangsu of China

Wang

Fang²,

Tang³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Medical diagnostic X-ray workers are one occupational group that expose to the long-term low-dose external radiation over their working lifetime, and they may under risk of different cancers. This study aims to determine the relationship between the occupational X-ray radiation exposure and cancer risk among these workers in Jiangsu, China. We conducted Nested case-control study to investigate the occupational X-ray radiation exposure and cancer risk. Data were collected through self-administered questionnaire, which includes but not limits to demographic data, personal behaviors and family history of cancer. Retrospective dose reconstruction was conducted to estimate the cumulative doses of the x-ray workers. Inferential statistics, t-test and 2 tests were used to compare the differences between each group. We used the logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of cancer by adjusting the age, gender. All 34 breast cancer cases and 45 esophageal cancer cases that detected in a cohort conducted among health workers between 1950~2011 were included in this presented study, and 158 cancer-free controls were selected by frequency-matched (1:2). Our study found that the occupational radiation exposure was associated with a significantly increased cancer risk compared with the control, especially in breast cancer and esophageal cancer (adjusted OR=2.90, 95% CI: 1.19-7.04 for breast cancer; OR=4.19, 95% CI: 1.87-9.38 for esophageal cancer, and OR=3.43, 95% CI: 1.92-6.12 for total cancer, respectively). The occupational X-ray radiation exposure was associated with increasing cancer risk, which indicates that proper intervention and prevention strategies may be needed in order to bring down the occupational cancer risk.

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DNA sequence analysis ofhprt mutants persisting in peripheral blood of cynomolgus monkeys more than two years after ENU treatment

Harbach¹,

Mattano²,

Zimmer³

et al. 1999

Environ. Mol. Mutagen.

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In vivo mutagenesis in the cynomolgus monkey: Time course ofHPRT mutant frequency at long time points following ethylnitrosourea exposure

Cited by 10 publications

References 17 publications

Lack of response to multiple genotoxic agents at the hprt locus in peripheral blood T‐lymphocytes of cynomolgus monkeys

Lack of response to multiple genotoxic agents at the hprt locus in peripheral blood T‐lymphocytes of cynomolgus monkeys

Nested Case-control Study of Occupational Radiation Exposure and Breast and Esophagus Cancer Risk among Medical Diagnostic X Ray Workers in Jiangsu of China

DNA sequence analysis ofhprt mutants persisting in peripheral blood of cynomolgus monkeys more than two years after ENU treatment

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