Relevance Of Animal Studies To The Evaluation Of Human Cancer Risk

Since its discovery in 1960 as a contaminant of poliovaccines, Simian Virus 40 (SV40) has been the object of extensive studies to assess whether this oncogenic virus plays a role in human carcinogenesis. Over the last two decades, this question has met with broad scepticism. However, there is increasing evidence linking SV40 to specific types of human cancer, especially malignant mesothelioma. Recently, two laboratories using different experimental approaches independently confirmed that SV40 acts synergistically with environmental fibers to promote mesothelial cell transformation and mesothelioma. Most of the scepticism concerning SV40 and cancer was due to the lack of clear epidemiologic data. However, it is still not clear how SV40 circulates in the human population, making the identification of SV40-exposed versus non-exposed cohorts problematic. Consequently, the most helpful insights into SV40-mediated carcinogenesis have come from molecular pathology, cell and molecular biology, and from animal studies.

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Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: A narrative review of the scientific literature

F1000Research ◽

10.12688/f1000research.20062.2 ◽

2020 ◽

Vol 8 ◽

pp. 1586

Author(s):

Leonie R. Price ◽

Javier Martinez

Keyword(s):

Cardiovascular Risk ◽

Cancer Progression ◽

Animal Studies ◽

Scientific Literature ◽

Human Cancer ◽

Narrative Review ◽

Nicotine Exposure ◽

Health Related

The emergence of new tobacco heating products and electronic nicotine delivery systems (ENDS) is changing the way humans are exposed to nicotine. The purpose of this narrative review is to provide a broad overview of published scientific literature with respect to the effects of nicotine on three key health-related areas: 1) cardiovascular risk, 2) carcinogenesis and 3) reproductive outcomes. These areas are known to be particularly vulnerable to the effects of cigarette smoke, and in addition, nicotine has been hypothesized to play a role in disease pathogenesis. Acute toxicity will also be discussed. The literature to February 2019 suggests that there is no increased cardiovascular risk of nicotine exposure in consumers who have no underlying cardiovascular pathology. There is scientific consensus that nicotine is not a direct or complete carcinogen, however, it remains to be established whether it plays some role in human cancer propagation and metastasis. These cancer progression pathways have been proposed in models in vitro and in transgenic rodent lines in vivo but have not been demonstrated in cases of human cancer. Further studies are needed to determine whether nicotine is linked to decreased fertility in humans. The results from animal studies indicate that nicotine has the potential to act across many mechanisms during fetal development. More studies are needed to address questions regarding nicotine exposure in humans, and this may lead to additional guidance concerning new ENDS entering the market.

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Epidemiologic Approaches to Assessing Human Cancer Risk from Consuming Aquatic Food Resources from Chemically Contaminated Water

Environmental Health Perspectives ◽

10.2307/3430858 ◽

1991 ◽

Vol 90 ◽

pp. 141 ◽

Cited By ~ 5

Author(s):

David Ozonoff ◽

Matthew P. Longnecker

Keyword(s):

Cancer Risk ◽

Human Cancer ◽

Food Resources ◽

Contaminated Water ◽

Aquatic Food

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Application of biochar to soils may result in plant contamination and human cancer risk due to exposure of polycyclic aromatic hydrocarbons

Environment International ◽

10.1016/j.envint.2018.09.010 ◽

2018 ◽

Vol 121 ◽

pp. 169-177 ◽

Cited By ~ 27

Author(s):

Jian Wang ◽

Kang Xia ◽

Michael Gatheru Waigi ◽

Yanzheng Gao ◽

Emmanuel Stephen Odinga ◽

...

Keyword(s):

Polycyclic Aromatic Hydrocarbons ◽

Cancer Risk ◽

Aromatic Hydrocarbons ◽

Human Cancer ◽

Polycyclic Aromatic ◽

Plant Contamination

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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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