The majority of malignant cells present genetic instability with chromosome number changes plus segmental defects: these changes involve intact chromosomes and breakage-induced alterations. Some pathways of chromosomal instability have been proposed as random breakage, telomere fusion, and centromere fission. Chromosome alterations in tumor cells have been described in animal models and in vitro experiments. One important question is about possible discrepancies between animal models, in vitro studies, and the real events in cancer cells in vivo. Papillomaviruses are relevant agents in oncogenic processes related to action on host genome. Recently, many reports have discussed the presence of virus DNA in peripheral blood, in humans and in animals infected by papillomaviruses. The meaning of this event is of controversy: possible product of apoptosis occurring in cancer cells, metastasized cancer cells, or active DNA sequences circulating in bloodstream. This study compares chromosome aberrations detected in bovine cells, in peripheral blood cells, and in BPV lesion cells: the literature is poor in this type of study. Comparing chromosome aberrations described in the different cells, a common mechanism in their origin, can be suggested. Furthermore blood cells can be evaluated as an effective way of virus transmission. 1. Introduction The papillomaviruses (PVs) are viruses that require the environment of a differentiating epithelium for their replication cycle [1]. PVs infect mammals, including man, and are related to development of benign lesions that can progress to cancer [2]. Uterine cervical cancer, the second most frequently occurring cancer in women worldwide, is causal related to human papillomavirus infection (HPV) [3, 4]. The Papillomavirus genome comprises three regions: LCR, “long control region” responsible for genome transcription control, L region, encoding the capsid major and minor proteins (L1 and L2, resp.), presenting late transcription in virus replication cycle, and E region, with early transcription in virus cycle, which codifies the proteins related to carcinogenic action [5, 6]. The virus transmission is recognized as occurring through direct contact: the abrasion of the skin or sexual intercourse leads to PV infection [7]. PV oncoproteins are the source for the alterations related to carcinogenesis: they interfere with the host cell cycle control, through interactions with specific proteins, as p53, p RB, p21, and p27 [8]. As examples of viral oncoprotein actions, E6 induces accelerated degradation of p53 [9]. E7 binds and
References
[1]
G. Borzacchiello and F. Roperto, “Bovine papillomaviruses, papillomas and cancer in cattle,” Veterinary Research, vol. 39, no. 5, article 45, 2008.
[2]
M. S. Campo, “Bovine papillomavirus and cancer,” Veterinary Journal, vol. 154, no. 3, pp. 175–188, 1997.
[3]
S. Duensing and K. Münger, “The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability,” Cancer Research, vol. 62, no. 23, pp. 7075–7082, 2002.
[4]
S. Duensing, L. Y. Lee, A. Duensing et al., “The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 18, pp. 10002–10007, 2000.
[5]
M. Kadaja, H. Isok-Paas, T. Laos, E. Ustav, and M. Ustav, “Mechanism of genomic instability in cells infected with the high-risk human papillomaviruses,” PLoS Pathogens, vol. 5, no. 4, 2009.
[6]
N. A. Hamid, C. Brown, and K. Gaston, “The regulation of cell proliferation by the papillomavirus early proteins,” Cellular and Molecular Life Sciences, vol. 66, no. 10, pp. 1700–1717, 2009.
[7]
V. Kashyap and B. C. Das, “DNA aneuploidy and infection of human papillomavirus type 16 in preneoplastic lesions of the uterine cervix: correlation with progression to malignancy,” Cancer Letters, vol. 123, no. 1, pp. 47–52, 1998.
[8]
D. Patel, A. Incassati, N. Wang, and D. J. McCance, “Human papillomavirus type 16 E6 and E7 cause polyploidy in human keratinocytes and up-regulation of G2-M-phase proteins,” Cancer Research, vol. 64, no. 4, pp. 1299–1306, 2004.
[9]
G. Boulet, C. Horvath, D. V. Broeck, S. Sahebali, and J. Bogers, “Human papillomavirus: E6 and E7 oncogenes,” International Journal of Biochemistry and Cell Biology, vol. 39, no. 11, pp. 2006–2011, 2007.
[10]
V. O'Brien, G. J. Grindlay, and M. S. Campo, “Cell transformation by the E5/E8 protein of bovine papillomavirus type 4. p27Kip1, elevated through increased protein synthesis, is sequestered by cyclin D1-CDK4 complexes,” Journal of Biological Chemistry, vol. 276, no. 36, pp. 33861–33868, 2001.
[11]
A. A. McBride, J. G. Oliveira, and M. G. McPhillips, “Partitioning viral genomes in mitosis: same idea, different targets,” Cell Cycle, vol. 5, no. 14, pp. 1499–1502, 2006.
[12]
J. G. Oliveira, L. A. Colf, and A. A. McBride, “Variations in the association of papillomavirus E2 proteins with mitotic chromosomes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 4, pp. 1047–1052, 2006.
[13]
S. Duensing and K. Münger, “Human papillomaviruses and centrosome duplication errors: modeling the origins of genomic instability,” Oncogene, vol. 21, no. 40, pp. 6241–6248, 2002.
[14]
R. C. Recouso, R. C. Stocco dos Santos, R. Freitas et al., “Clastogenic effect of bracken fern (Pteridium aquilinum aracnoideum) diet in peripheral lymphocytes of human consumers: preliminary data,” Veterinary and Comparative Oncology, vol. 1, no. 1, pp. 22–29, 2003.
[15]
R. C. Stocco Dos Santos, C. J. Lindsey, O. P. Ferraz et al., “Bovine papillomavirus transmission and chromosomal aberrations: an experimental model,” Journal of General Virology, vol. 79, no. 9, pp. 2127–2135, 1998.
[16]
A. C. De Freitas, C. De Carvalho, O. Brunner et al., “Viral DNA sequences in peripheral blood and vertical transmission of the virus: a discussion about BPV-1,” Brazilian Journal of Microbiology, vol. 34, no. 1, pp. 76–78, 2003.
[17]
C. J. Lindsey, M. E. Almeida, C. F. Vicari et al., “Bovine papillomavirus DNA in milk, blood, urine, semen, and spermatozoa of bovine papillomavirus-infected animals,” Genetics and Molecular Research, vol. 8, no. 1, pp. 310–318, 2009.
[18]
S. Roperto, R. Brun, F. Paolini et al., “Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role,” Journal of General Virology, vol. 89, no. 12, pp. 3027–3033, 2008.
[19]
T. C. Melo, N. Diniz, S. R. C. Campos et al., “Cytogenetic studies in peripheral blood of bovines afflicted by papillomatosis,” Veterinary and Comparative Oncology, vol. 9, no. 4, pp. 269–274, 2011.
[20]
J. W. Moura, R. C. Stocco Dos Santos, M. L. Z. Dagli, J. L. D'Angelino, E. H. Birgel, and W. Becak, “Chromosome aberrations in cattle raised on bracken fern pasture,” Experientia, vol. 44, no. 9, pp. 785–788, 1988.
[21]
M. B. Lioi, R. Barbieri, G. Borzacchiello et al., “Chromosome aberrations in cattle with chronic enzootic haematuria,” Journal of Comparative Pathology, vol. 131, no. 2-3, pp. 233–236, 2004.
[22]
C. De Carvalho, A. C. De Freitas, O. Brunner et al., “Bovine papillomavirus type 2 in reproductive tract and gametes of slaughtered bovine females,” Brazilian Journal of Microbiology, vol. 34, no. 1, pp. 82–84, 2003.
[23]
A. Yaguiu, C. Carvalho, A. C. Freitas, et al., “Papilomatosis in cattle: in situ detection of bovine papillomavirus DNA sequences in reproductive tissues,” Brazilian Journal of Morphological Sciences, vol. 23, no. 3-4, pp. 525–529, 2006.
[24]
A. Yaguiu, M. L. Z. Dagli, E. H. Birgel Jr. et al., “Simultaneous presence of bovine papillomavirus and bovine leukemia virus in different bovine tissues: in situ hybridization and cytogenetic analysis,” Genetics and Molecular Research, vol. 7, no. 2, pp. 487–497, 2008.
[25]
M. S. Campo, W. F. H. Jarrett, W. O'Neil, and R. J. Barron, “Latent papillomavirus infection in cattle,” Research in Veterinary Science, vol. 56, no. 2, pp. 151–157, 1994.
[26]
V. Peretti, F. Ciotola, S. Albarella et al., “Chromosome fragility in cattle with chronic enzootic haematuria,” Mutagenesis, vol. 22, no. 5, pp. 317–320, 2007.
[27]
T. Ogawa, Y. Tomita, M. Okada et al., “Broad-spectrum detection of papillomaviruses in bovine teat papillomas and healthy teat skin,” Journal of General Virology, vol. 85, no. 8, pp. 2191–2197, 2004.
[28]
A. M. Leal, O. P. Ferraz, C. Carvalho et al., “Quercetin induces structural chromosome aberrations and uncommon rearrangements in bovine cells transformed by the E7 protein of bovine papillomavirus type 4,” Veterinary and Comparative Oncology, vol. 1, no. 1, pp. 15–21, 2003.
[29]
A. Duensing, A. Chin, L. Wang, S.-F. Kuan, and S. Duensing, “Analysis of centrosome overduplication in correlation to cell division errors in high-risk human papillomavirus (HPV)-associated anal neoplasms,” Virology, vol. 372, no. 1, pp. 157–164, 2008.
[30]
Z. Liu, Y. Liu, Y. Hong, L. Rapp, E. J. Androphy, and J. J. Chen, “Bovine papillomavirus type 1 E6-induced sensitization to apoptosis is distinct from its transforming activity,” Virology, vol. 295, no. 2, pp. 230–237, 2002.
[31]
S. R. C. Campos, C. Trindade, O. P. Ferraz et al., “Can established cultured papilloma cells harbor bovine papillomavirus?” Genetics and Molecular Research, vol. 7, no. 4, pp. 1119–1126, 2008.
