Influence of age, sex and strain on the in vitro induction of unscheduled dna synthesis in rat hepatocyte primary cultures
Tóm tắt
The activity of chemical-induced unscheduled DNA synthesis was evaluated in hepatocyte primary cultures from Fischer 344 and Sprague-Dawley rats over a period of two years. In this two-year study hepatocytes from both sexes and strains were prepared from animals 2, 8, 14, 20 and 25 months of age and UDS was measured by autoradiography following treatment with N-methyl-AP-vitro-N-nitrosoguanidine and 2-acetylaminofluorine. A dose-related positive response occurred for both compounds throughout the study in hepatocytes from male and female Fischer rats and male Sprague-Dawley rats. The magnitude of the response was greatest in hepatocytes from male Fischer rats and a markedly lower response in unscheduled DNA synthesis occurred in all cultures prepared from animals of both strains and sexes at 20 and 25 months of age. Hepatocytes from female Sprague-Dawley rats showed a low level of unscheduled DNA synthesis with N-methylN′-vitro-N-nitrosoguanidine throughout the study. The most striking finding was the absence of a UDS response to 2-acetylaminofuorene by hepatocytes from Sprague-Dawley females at the 8, 14, 20 or 25 month periods. The results indicate an age-related decrease in chemical-induced unscheduled DNA synthesis activity among rats.
Tài liệu tham khảo
BELAND, F.A., DOOLEY, K.L. and JACKSON, C.D. (1982). Persistence of DNA adducts in rat liver and kidney after multiple doses of the carcinogen N-hydroxy-2-acetylaminofluorene. Cancer Res. 42:1348–1354.
HALL, J.D., ALMY, R.E. and SCHERER, K. L. (1982). DNA repair in cultured human fibroblasts does not decline with donor age. Exp. Cell Res. 139:351–359.
HAMM, T.E., Jr. (1983). The occurrence of neoplasms in long-term in vivo studies. In: Application of Biological Markers to Carcinogen Testing (H.A. Milmen and S. Sell eds.), pp. 9–23, Plenum Publishing Corp., New York.
HART, R.W., SACHAR, G.A. and Hoskins, T.L. (1979). DNA repair in a short- and long-lived rodent species. J. Gerontol. 34:808–817.
HART, R.W. and SETLOW, R.B. (1974). Correlation between deoxyribonucleic acid excision repair and lifespan. Proc. Natl. Acad. Sci. 71:2169–2173.
HENNIS, H.L., BRAID, H.L. and RUSELL, V.A. (1981). Unscheduled DNA synthesis in cells of different shape in fibroblast cultures from donors of various ages. Mech. Aging Dev. 16:355–361.
HOWARD, P.C., CASCIANO, D.A., BELAND, F.A. and SHADDOCK, J.F., Jr. (1981). The binding of N-hydroxy-2-acetylaminofluorene to DNA and repair of the adducts of primary rat hepatocyte cultures. Carcinogenesis 2:97–102.
IRVING, C.C. (1975). Comparative toxicity of N-hydroxy-2-acetylaminofluorene in several strains of rats. Cancer Res. 35:2959–2961.
KORNBRUST, D.J. and BARFKNECHT, T.R. (1984). Comparison of rat and hamster hepatocyte primary culture/ DNA repair assays. Environ. Mutagen. 6:1–11.
LAMBERT, B., RINGBORG, U. and SKOOG, L. (1979). Age-related decrease of ultraviolet light-induced DNA repair synthesis in human peripheral lymphocytes. Cancer Res. 39:2792–2795.
LIU, S.C., PARSONS, C.S. and HANAWALT, P.C. (1982). DNA repair in human epidermal keratinocytes from donors of different age. J. Invert. Dermatol. 78:330–335.
MASLANSKY, C.J. and WILLIAMS, G.M. (1985). Ultraviolet light-induced DNA repair synthesis in hepatocytes from species of differing longevities. Mech. Aging Dev. 9:191–203.
NETTE, E.G., XI, Y.P., SUN, Y.K., ANDREWS, A.D. and KING, D.W. (1984). A correlation between aging and DNA repair in human epidermal cells. Mech. Aging Dev. 24:283–292.
PAFFENHOLZ, V. (1978). Correlation between DNA repair of embryonic fibroblasts and different lifespan of three inbred mouse strains. Mech. Aging Dev. 7:131–150.
PLESKO, M.M. and RICHARDSON, A. (1984). Age-related changes in unscheduled DNA synthesis by rat hepatocytes. Biochem. Biophys. Res. Commun. 118:730–735.
PROBST, G.S., MCMAHON, R.E., HILL, L.E., THOMPSON, C.Z., EPP, J.K. and NEAL, S.B. (1981). Chemically induced unscheduled DNA synthesis in primary rat hepatocyte cultures: A comparison with bacterial mutagenicity using 218 compounds. Environ. Mutagen. 3:11–32.
WILLIAMS, G. M. (1977). Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures. Cancer Res. 37:1845–1851.
WILLIAMS, G. M. and GUNN, J. M. (1974). Long-term cell culture of adult rat liver epithelial cells. Exp. Cell Res. 89:139–142.