Neoplastic and Nonneoplastic Lesions in Aging Mice of Unique and Common Inbred Strains Contribution to Modeling of Human Neoplastic Diseases

Szymańska, Hanna; Lechowska-Piskorowska, J.; Krysiak, E.; Strzałkowska, Adriana; Unrug-Bielawska, Katarzyna; Grygalewicz, Beata; Skurzak, H; Pieńkowska-Grela, Barbara; Gajewska, Marta

doi:10.1177/0300985813501334

Cited by 34 publications

(30 citation statements)

References 53 publications

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“…This suggests that the extraoral masses are likely independent primary neoplasms rather than metastases from the oral lesions. Szymanska et al (2014) documented that C57BL/6 mice are prone to hematopoietic cancers and malignant lymphomas with age. However, we did not observe such tumor masses in age-matched, non-carcinogen-exposed controls.…”

Section: Discussionmentioning

confidence: 99%

Impact of Age on Disease Progression and Microenvironment in Oral Cancer

et al. 2018

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Despite the recognized link between aging and cancer, most preclinical studies in experimental tumor models are conducted with 6- to 8-wk-old rodents. The goal of the present study was to examine the impact of age on tumor incidence, growth, and microenvironmental characteristics in mouse models of head and neck squamous cell carcinoma (HNSCC). Experimental studies were conducted with the 4-nitroquinoline-oxide (4NQO) oral carcinogenesis model and orthotopic FaDu HNSCC xenografts, established in young (7 to 12 wk of age) and old (65 to 70 wk of age) female C57BL/6 mice ( n = 44; 4NQO model) and severe combined immunodeficient mice ( n = 13; HNSCC xenografts). Noninvasive whole body magnetic resonance imaging revealed increased subcutaneous and visceral fat in aging animals of both strains. On histologic examination, a higher incidence ( P < 0.001) of severe dysplasia/invasive squamous cell carcinoma was observed in old mice (92%) as compared with young mice (69%). Old C57BL/6 mice exposed to 4NQO exhibited increased incidence of oral and extraoral (peritoneal masses) neoplasms (42%) versus their young counterparts ( P < 0.05). The incidence of extraoral neoplasms was significantly lower (16%) in the younger cohort. Interestingly, no difference in growth rate and oxygen saturation was observed between orthotopic FaDu xenografts established in old and young severe combined immunodeficient mice. Our observations suggest that host age may have an impact on the growth kinetics and progression of HNSCC in the immunocompetent 4NQO model. Further investigation into the impact of aging on tumor response to preventive and therapeutic intervention is warranted.

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Section: Discussionmentioning

confidence: 99%

Impact of Age on Disease Progression and Microenvironment in Oral Cancer

et al. 2018

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“…In previous literature, few or no articles reported on sperm granulomas occurring in the epididymis of relatively young C57BL/6N mice (10 and 13 weeks old). In a study that presents historical data on the aging mice of inbred strains (129S1/SvW, A.CA-H2 f /W, AKR/W, BALB/cW, BN/aW, C57BL/6 W, C57BL/10 W, C3Hwad/W, C3H wad /W, CBA/W, DBA/2W, WOM/W and B6; 129), sperm granuloma did not occurred [ 5 6 ]. In CByB6F1-Tg(HRAS)2Jic mice, which are often employed as animal models for studying the carcinogenicity replacement, approximately 0~8% of sperm granuloma was reported [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Higher incidence of sperm granuloma in the epididymis of C57BL/6N mice

et al. 2018

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C57BL/6N mice are inbred strains widely used in biomedical research. Hence, a large amount of basic data has been accumulated. However, in the field of histopathology, spontaneous data for relatively younger mice that are used more frequently are not yet abundant, in contrast to data for older mice and their neoplastic lesions. To acquire the essential background data required by various research and toxicological assessments, 120 mice of the C57BL/6N strain (10 and 13 weeks of age) were collected from two institutions (From Korea and Japan) and subjected to histopathological analyses of the major organs (liver, spleen, kidney, thymus, heart, testis, epididymis). The results showed significantly higher incidence of sperm granulomas in the epididymides (10-56%) of these mice, compared with that in other strains or species of lab animals. Upon closer inspection, oligospermia/clear cell hyperplasia, cellular debris, and tubular vacuolation were also observed in the epididymides with sperm granulomas. Moreover, diseased organs were significantly heavier than healthy ones. Immunohistochemical staining showed a significant increase in the chromatic figures of cysteine-dependent aspartate-directed proteases-3 (caspase-3) and cleaved-poly(ADP-ribose) polymerase (c-PARP), and damages to the tubule due to spontaneous apoptosis, which may have led to the sperms leaking out of the tubule, causing the granuloma. To conclude, spontaneous sperm granuloma can occur in 10- and 13-week-old C57BL/6N mice and may thus affect the results of various studies using these mice. Therefore, sperm granuloma in epididymis needs to be carefully considered as an important factor when design the study using C57BL/6N.

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“…Judging by size and longevity, mice should be at low risk of cancer. However, in captivity, whereby mice can survive into old ages, they reveal rather higher susceptibility to cancer, with 50%–90% of old mice dying of cancer (Ikeno et al, 2009; Lipman, Galecki, Burke, & Miller, 2004; Szymanska et al, 2014; Ward, 1983). One caveat to this statistic, though, is that it is unclear how much the highly inbreed nature of laboratory mice contributes to cancer susceptibility.…”

Section: Life History‐dependent and Species‐specific Evolution Of Genmentioning

confidence: 99%

The three dimensions of somatic evolution: Integrating the role of genetic damage, life‐history traits, and aging in carcinogenesis

Rozhok

DeGregori

2020

Evolutionary Applications

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Tumors result from genetic and epigenetic alterations that change cellular survival and differentiation probabilities, promoting clonal dominance. Subsequent genetic and selection processes in tumors allow cells to lose their tissue fidelity and migrate to other parts of the body, turning tumors into cancer. However, the relationship between genetic damage and cancer is not linear, showing remarkable and sometimes seemingly counterintuitive patterns for different tissues and across animal taxa. In the present paper, we attempt to integrate our understanding of somatic evolution and cancer as a product of three major orthogonal processes: occurrence of somatic mutations, evolution of species‐specific life‐history traits, and physiological aging. Patterns of cancer risk have been shaped by selective pressures experienced by animal populations over millions of years, influencing and influenced by selection acting on traits ranging from mutation rate to reproductive strategies to longevity. We discuss how evolution of species shapes their cancer profiles alongside and in connection with other evolving life‐history traits and how this process explains the patterns of cancer incidence we observe in humans and other animals.

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Neoplastic and Nonneoplastic Lesions in Aging Mice of Unique and Common Inbred Strains Contribution to Modeling of Human Neoplastic Diseases

Cited by 34 publications

References 53 publications

Impact of Age on Disease Progression and Microenvironment in Oral Cancer

Impact of Age on Disease Progression and Microenvironment in Oral Cancer

Higher incidence of sperm granuloma in the epididymis of C57BL/6N mice

The three dimensions of somatic evolution: Integrating the role of genetic damage, life‐history traits, and aging in carcinogenesis

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