Differential effect of parity on rat mammary carcinogenesis after pre- or post-pubertal exposure to radiation

Takabatake, Masaru; Daino, Kazuhiro; Imaoka, Tatsuhiko; Blyth, Benjamin J.; Kokubo, Toshiaki; Nishimura, Yukiko; Showler, Kaye; Hosoki, Ayaka; Moriyama, Hitomi; Nishimura, Masaharu; Kakinuma, Shizuko; Fukushi, Masahiro; Shimada, Yoshiya

doi:10.1038/s41598-018-32406-1

Cited by 12 publications

(17 citation statements)

References 63 publications

(80 reference statements)

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“…Notably, the subtype of breast cancer is influenced by various factors such as the number of births and obesity, and differences in these reproductive and lifestyle factors might underlie the inconsistency among the reported results (23). On the other hand, rats mainly develop hormone receptor-positive mammary carcinomas in both spontaneous and chemical-induced models (6,17). Our present data concerning subtype frequency are consistent with published data (17).…”

Section: Discussionsupporting

confidence: 92%

“…On the other hand, rats mainly develop hormone receptor-positive mammary carcinomas in both spontaneous and chemical-induced models (6,17). Our present data concerning subtype frequency are consistent with published data (17).…”

Section: Discussionsupporting

confidence: 92%

“…We have previously conducted a series of experiments to quantify the incidence of neutron-induced mammary carcinomas in rats (16,17). In our present study, we further analysed the mammary carcinomas from those experiments Immunostaining and classification of tumor subtypes.…”

Section: Abstract Background/aim: Neutrons Are Used As a Type Of Higmentioning

confidence: 99%

“…In our present study, we further analysed the mammary carcinomas from those experiments Immunostaining and classification of tumor subtypes. Formalinfixed, paraffin-embedded tissue sections were immunostained with antibodies against the estrogen receptor (ER) α (clone 6F11, Leica Biosystems, Nussloch, Germany; dilution, 1:400), the progesterone receptor (PgR; clone SP42, Acris Antibodies, Herford, Germany; 1:400), HER2 (a mixture of clones e2-4001 and 3B5, Thermo Fisher Scientific, Waltham, MA, USA; 1:100), and the proliferation marker Ki-67 (clone SP6, Spring Bioscience, Pleasanton, CA, USA; 1:200) as previously described (17). Each slide was scanned using a NanoZoomer XR C12000-03 slide scanner (Hamamatsu Photonics, Hamamatsu, Japan), and all images were saved in NDPI format.…”

Section: Abstract Background/aim: Neutrons Are Used As a Type Of Higmentioning

confidence: 99%

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Neutron-induced Rat Mammary Carcinomas Are Mainly of Luminal Subtype and Have Multiple Copy Number Aberrations

Moriyama¹,

Daino²,

Imaoka³

et al. 2019

Anticancer Res

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to understand the subtype(s) of these carcinomas for which the incidence was increased following neutron exposure. We also clarified the DNA copy number aberrations of these mammary carcinomas to elucidate the mechanisms of neutron-induced carcinogenesis. Materials and Methods Tissue samples. Tumor samples were obtained from our previous study (8), which was approved by the Institutional Animal Care and Use Committee of National Institute of Radiological Sciences. Briefly, in that previous study, 7-week-old female Jcl:SD rats (Clea Japan Inc., Tokyo, Japan) were whole-body irradiated with 9 Be(d,nγ) 10 B fast neutrons (mean energy, 2 MeV) or 137 Cs γ rays, and mammary carcinoma development was assessed by weekly palpation until the age of 90 weeks. All of the carcinomas available from the neutron-irradiated (0.485 Gy, n=16), γ-ray-irradiated (0.5 Gy, n=14), and the matched untreated rats (n=28), excluding the ones from rats found dead, were analysed.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Abstract Background/aim: Neutrons Are Used As a Type Of Higmentioning

confidence: 99%

Section: Abstract Background/aim: Neutrons Are Used As a Type Of Higmentioning

confidence: 99%

See 2 more Smart Citations

Neutron-induced Rat Mammary Carcinomas Are Mainly of Luminal Subtype and Have Multiple Copy Number Aberrations

Moriyama¹,

Daino²,

Imaoka³

et al. 2019

Anticancer Res

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“…Second, young adult (7-week-old) male mice were used in the present study. It has been reported that biological radiation effects vary with age and sex 36,37 . Further studies should examine whether age and sex affect radiation-induced antioxidant changes.…”

Section: Discussionmentioning

confidence: 99%

Total body irradiation causes a chronic decrease in antioxidant levels

Sun

Inaba

Sogo

et al. 2021

Sci Rep

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Ionizing radiation exposure may not only cause acute radiation syndrome, but also an increased risk of late effects. It has been hypothesized that induction of chronic oxidative stress mediates the late effects of ionizing radiation. However, only a few reports have analyzed changes in long-term antioxidant capacity after irradiation in vivo. Our previous study demonstrated changes in whole-blood antioxidant capacity and red blood cell (RBC) glutathione levels within 50 days after total body irradiation (TBI). In this study, seven-week-old, male, C57BL/6J mice exposed to total body irradiation by X-ray and changes in whole-blood antioxidant capacity and RBC glutathione levels at ≥ 100 days after TBI were investigated. Whole-blood antioxidant capacity was chronically decreased in the 5-Gy group. The RBC reduced glutathione (GSH) level and the GSH/oxidative glutathione (GSSG) ratio were chronically decreased after ≥ 1 Gy of TBI. Interestingly, the complete blood counts (CBC) changed less with 1-Gy exposure, suggesting that GSH and the GSH/GSSG ratio were more sensitive radiation exposure markers than whole-blood antioxidant capacity and CBC counts. It has been reported that GSH depletion is one of the triggers leading to cataracts, hypertension, and atherosclerosis, and these diseases are also known as radiation-induced late effects. The present findings further suggest that chronic antioxidant reduction may contribute to the pathogenesis of late radiation effects.

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Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast

Helm

Rudel

2020

Arch Toxicol

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Knowledge about established breast carcinogens can support improved and modernized toxicological testing methods by identifying key mechanistic events. Ionizing radiation (IR) increases the risk of breast cancer, especially for women and for exposure at younger ages, and evidence overall supports a linear dose-response relationship. We used the Adverse Outcome Pathway (AOP) framework to outline and evaluate the evidence linking ionizing radiation with breast cancer from molecular initiating events to the adverse outcome through intermediate key events, creating a qualitative AOP. We identified key events based on review articles, searched PubMed for recent literature on key events and IR, and identified additional papers using references. We manually curated publications and evaluated data quality. Ionizing radiation directly and indirectly causes DNA damage and increases production of reactive oxygen and nitrogen species (RONS). RONS lead to DNA damage and epigenetic changes leading to mutations and genomic instability (GI). Proliferation amplifies the effects of DNA damage and mutations leading to the AO of breast cancer. Separately, RONS and DNA damage also increase inflammation. Inflammation contributes to direct and indirect effects (effects in cells not directly reached by IR) via positive feedback to RONS and DNA damage, and separately increases proliferation and breast cancer through pro-carcinogenic effects on cells and tissue. For example, gene expression changes alter inflammatory mediators, resulting in improved survival and growth of cancer cells and a more hospitable tissue environment. All of these events overlap at multiple points with events characteristic of "background" induction of breast carcinogenesis, including hormone-responsive proliferation, oxidative activity, and DNA damage. These overlaps make the breast particularly susceptible to ionizing radiation and reinforce that these biological activities are important characteristics of carcinogens. Agents that increase these biological processes should be considered potential breast carcinogens, and predictive methods are needed to identify chemicals that increase these processes. Techniques are available to measure RONS, DNA damage and mutation, cell proliferation, and some inflammatory proteins or processes. Improved assays are needed to measure GI and chronic inflammation, as well as the interaction with hormonally driven development and proliferation. Several methods measure diverse epigenetic changes, but it is not clear which changes are relevant to breast cancer. In addition, most toxicological assays are not conducted in mammary tissue, and so it is a priority to evaluate if results from other tissues are generalizable to breast, or to conduct assays in breast tissue. Developing and applying these assays to identify exposures of concern will facilitate efforts to reduce subsequent breast cancer risk.Biological systems studied This review article summarizes and synthesizes data from cell-culture, experimental animals, and human epidem...

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Differential effect of parity on rat mammary carcinogenesis after pre- or post-pubertal exposure to radiation

Cited by 12 publications

References 63 publications

Neutron-induced Rat Mammary Carcinomas Are Mainly of Luminal Subtype and Have Multiple Copy Number Aberrations

Neutron-induced Rat Mammary Carcinomas Are Mainly of Luminal Subtype and Have Multiple Copy Number Aberrations

Total body irradiation causes a chronic decrease in antioxidant levels

Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast

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