Evaluating the sensitivity of newborn rats and newborn hamsters to oncogenic DNA.

Autor: Sheng-Fowler L; Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA., Tu W; Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA., Phy K; Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA., Macauley J; Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA., Lanning L; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20888, USA., Lewis AM Jr; Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA., Peden K; Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA. Electronic address: keith.peden@fda.hhs.gov.
Jazyk: angličtina
Zdroj: Biologicals : journal of the International Association of Biological Standardization [Biologicals] 2023 Nov; Vol. 84, pp. 101724. Date of Electronic Publication: 2023 Nov 16.
DOI: 10.1016/j.biologicals.2023.101724
Abstrakt: To evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cell lines, we have been establishing in vivo assays to quantify the oncogenic activity of DNA. We had generated three oncogene-expression plasmids: pMSV-T24-H-ras, which expresses activated H-ras; pMSV-c-myc, which expresses c-myc; and pMSV-T24-H-ras/MSV-c-myc, which expresses both oncogenes. Tumors were induced in mice by pMSV-T24-H-ras plus pMSV-c-myc or by pMSV-T24-H-ras/MSV-c-myc. Because newborn hamsters and newborn rats have been recommended for oncogenicity testing of the DNA from tumorigenic mammalian cell-substrates used for vaccine production, we evaluated their sensitivity. Newborn hamsters and rats were inoculated with different doses of pMSV-T24-H-ras/MSV-c-myc to determine their sensitivity to tumor induction and with the single-oncogene-expression plasmids to determine whether single oncogenes could induce tumors. Newborn rats were more sensitive than newborn hamsters, and activated H-ras but not c-myc induced tumors in newborns of both rodent species. DNA from four cell lines established from tumors induced by pMSV-T24-H-ras/MSV-c-myc was inoculated into newborn rats. Because no tumors were induced by this cellular DNA, which should be optimal as it contains both oncogenes linked and present in several copies, we conclude that available in vivo models are not sensitive enough to detect the oncogenicity of cellular DNA.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE
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