Chemically contaminated aquatic food resources and human cancer risk: retrospective.

<em>Abstract.</em>—Much is known about the importance of the physical characteristics of salmonid habitat in Alaska and the Pacific Northwest, with far less known about the food sources and trophic processes within these habitats, and the role they play in regulating salmonid productivity. Freshwater food webs supporting salmonids in Alaska rely heavily on nutrient, detritus, and prey subsidies from both marine and terrestrial ecosystems. Adult salmon provide a massive input of marine biomass to riverine ecosystems each year when they spawn, die, and decompose, and are a critical food source for young salmon in late summer and fall; riparian forests provide terrestrial invertebrates to streams, which at times comprise over half of the food ingested by stream-resident salmonids; up-slope, fishless headwater streams are a year-round source of invertebrates and detritus for fish downstream. The quantity of these food resources vary widely depending on source, season, and spatial position within a watershed. Terrestrial invertebrate inputs from riparian habitats are generally the most abundant food source in summer. Juvenile salmonids in streams consume roughly equal amounts of freshwater and terrestrially-derived invertebrates during most of the growing season, but ingest substantial amounts of marine resources (salmon eggs and decomposing salmon tissue) when these food items are present. Quantity, quality, and timing of food resources all appear to be important driving forces in aquatic food web dynamics, community nutrition, and salmonid growth and survival in riverine ecosystems.

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Involvement of APOBEC3B in mutation induction by irradiation

Journal of Radiation Research ◽

10.1093/jrr/rraa069 ◽

2020 ◽

Vol 61 (6) ◽

pp. 819-827

Author(s):

Yohei Saito ◽

Hiromasa Miura ◽

Nozomi Takahashi ◽

Yoshikazu Kuwahara ◽

Yumi Yamamoto ◽

...

Keyword(s):

Dna Damage ◽

Cancer Risk ◽

Cell Line ◽

Human Cancer ◽

Spontaneous Mutation ◽

Mutation Induction ◽

Parent Cell ◽

Induced Mutations ◽

Parent Cell Line ◽

Radiation Induced

Abstract To better understand the cancer risk posed by radiation and the development of radiation therapy resistant cancer cells, we investigated the involvement of the cancer risk factor, APOBEC3B, in the generation of radiation-induced mutations. Expression of APOBEC3B in response to irradiation was determined in three human cancer cell lines by real-time quantitative PCR. Using the hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutation assay, mutations in the HPRT gene caused by irradiation were compared between APOBEC3B-deficient human hepatocellular carcinoma (HepG2) cells [APOBEC3B knocked out (KO) using CRISPR-Cas9 genome editing] and the parent cell line. Then, HPRT-mutated cells were individually cultured to perform PCR and DNA sequencing of HPRT exons. X-Irradiation induced APOBEC3B expression in HepG2, human cervical cancer epithelial carcinoma (HeLa) and human oral squamous cell carcinoma (SAS) cells. Forced expression of APOBEC3B increased spontaneous mutations. By contrast, APOBEC3B KO not only decreased the spontaneous mutation rate, but also strongly suppressed the increase in mutation frequency after irradiation in the parent cell line. Although forced expression of APOBEC3B in the nucleus caused DNA damage, higher levels of APOBEC3B tended to reduce APOBEC3B-induced γ-H2AX foci formation (a measure of DNA damage repair). Further, the number of γ-H2AX foci in cells stably expressing APOBEC3B was not much higher than that in controls before and after irradiation, suggesting that a DNA repair pathway may be activated. This study demonstrates that irradiation induces sustained expression of APOBEC3B in HepG2, HeLa and SAS cells, and that APOBEC3B enhances radiation-induced partial deletions.

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Biological Aging Marker p16INK4a in T Cells and Breast Cancer Risk

Cancers ◽

10.3390/cancers12113122 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3122

Author(s):

Jie Shen ◽

Renduo Song ◽

Bernard F. Fuemmeler ◽

Kandace P. McGuire ◽

Wong-Ho Chow ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Mrna Expression ◽

Cellular Senescence ◽

Human Cancer ◽

Biological Aging ◽

Increased Risk ◽

Discovery Stage

Prior research has demonstrated that altered telomere length, a well-known marker for biological aging, is associated with various types of human cancer. However, whether such association extends to additional hallmarks of biological aging, including cellular senescence, has not been determined yet. In this two-stage study, we assessed the association between p16INK4a mRNA expression in T cells, a marker of cellular senescence, and breast cancer risk. The discovery stage included 352 breast cancer patients and 324 healthy controls. p16INK4a mRNA expression was significantly higher in individuals who were older, Black, and had family history of cancer than their counterparts in both cases and controls. p16INK4a mRNA expression also differed by marital status, annual income, and smoking status in cases. In the discovery stage, we found that increased p16INK4a mRNA expression was associated with 1.40-fold increased risk of breast cancer (OR = 1.40; 95%CI: 1.21, 1.68; p < 0.001). A marginally significant association was further observed in the validation stage with 47 cases and 48 controls using pre-diagnostic samples (OR = 1.28; 95%CI: 0.98, 2.97; p = 0.053). In addition, we found that p16INK4a mRNA expression was higher in tumors with selected aggressive characteristics (e.g., poorly differentiated and large tumors) than their counterparts. In summary, our results demonstrate that higher p16INK4a mRNA expression in T cells is a risk factor for breast cancer and further support the role of biological aging in the etiology of breast cancer development. Novelty and Impact Statements: The results from this study provide evidence that cellular senescence, a process of biological aging, plays a role in breast cancer etiology. In addition, our results also support that social demographics may modify cellular senescence and biological aging.

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