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Council for Tobacco Research

Rna Tumor Virus Genomes As Determinants of Chemically Induced Transformation in Vitro [Explains Experiments on Effects of Chemicals and Leukemia Viruses As Inducers of Cell Transformation]

Date: 01 Sep 1971 (est.)
Length: 14 pages
CTRCONTRACTS002370-CTRCONTRACTS002383
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Abstract

MAR

Fields

Type
SCIENTIFIC REPORT
DRAFT
Master ID
Ctrcontracts00237
Request
58
Depository Date
31 May 1996
Named Person
Chen
Heidelberger
Rhim
Todaro
Weisburger, E., Nci
Weisburger, J., Nci
Author
Freeman, A.E., Mai
Huebner, R.J., Mai
Kelloff, G.J., Mai
Price, P.J., Mai
Zimmerman, E.M., Mai
Box
176
UCSF Legacy ID
zsk3aa00

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Tr''aat is the role of the chemical?:-- We believe that the chemical accelerates the rate of transformation by blocking or derepressing the host cell gene control mechanisms. Thus, chemical carcinogens alone would increase the rate of transforma- tion by der ess enous ,~ral oncoger.es a:1 :.m a few cases, synthesis of infectious virus may also be derepressed ( Tdhy do chemicals and viruses enhance each other as ` a::sforminz agents?:--in chronically infected cells, multiple copies of the oncogene are produced, but cannot usually induce tra,-isforr..ation due to the cell's repressor mechanisms. 'Under these conditions, inhibition of the cell's repressor mechanisms results in a h igh rate of transformation. G onclusion In conclusion we must make two final observations. First, although it is the virus which provided the oncogenic information, the chemicals are extremely important since they change the order of magnitude of the transformation rate. This means that events which would be seen but rarely in the lifeline of the animal would occur with higher frequency upon prolonged exposure to carcinogens. Secondly, regardless of the validity of our interpretation of the relative roles of chemical carcinogens and viruses, it seems probable that there is no such thing as a cell culture completely free of viral genetic information { } and those engaged with in vitro studies must take this into account.
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REFERENCES 1. FREEMAN, A.E., PRICE, P.3., T_GEL, H.J., YOU~i~, J.C., #1ARYAK. 3..?f., and KIJEB~'u'R, R.,°. . "_orphol og:ca? ..rars:or...ation of rat embryo ce__s induced by diethylnitrosamine and murine leukemia viruses. 3. -Nat. Cancer Inst. 44: 65-78 (1970). 2. PRICE, P.J., FREEYA1, A.E., LANE, W.T., and HUEBNER, R.J.: !•!orphological transformation of rat embryo cells by the combined action of 3-.:.ethyl- cholanthrene and Rauscher Ieukaemia•v£rus. Nature, N.B. 230: I44-146 (1971). 3. FREEMAN, A.E., PRICE, P.J., BRYALT, R.J., GORDON, R.3., GILDEN, R.V., KELLOFF, G.J., and HUEBNER, R.J.: Proc. Nat. Acad. Sci. 68: 445-449 (1971). 4. PRICE, P.J., FREEu:A-NT, A.E., LANE, W.T., RABSTEIN, L.F., VERNON, 14i.L., and HUEBNER, R.J.• In vitro transformation and activation of latent RNA viruses as indications of the carcinogenic activity of cigarette smoke condensates. In preparation. 5. RHIM, J.S., CHO, H.Y., J{}GLEKA.R, M.H., and HUEBNER, R.J.: Comparison of the transforming effect of benzo(a)pyrene in mammalian cell lines in vitro. In preparation. . 6. RFiIM, 3.S., VASS, k., CHO, H.Y., and HUEBNER, R.J.: Malignant transformation induced by 7,12-dimethylbenz(a)anthracene in rat embryo cells infected with Rauscher leukemia virus. Int. J. Cancer 7: 65-74 (1971). 7. BERWALH, Y., and SACHS, L.: In vitro transformation of normal cells to tumor cells by carcinogenic hydrocarbons. J. Nat. Cancer Inst. 35: 641-661 (1965).
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CHEN, T.T., and FTIDELBERGER, C.: Quantitative studies on the malignant trans fo in vitro. o:f mouse prostate cells by carcinogenic hydrocarbons Int. .7. Cancer 4: 166-178 (1969). 9. Er`liRLL, s+1.R. : C;,a;,t;es induced in a s:rain of fibroblas ts ..rom a strain C3H mouse by the action of 20-methylcholanthrene (preliminary report). J. Nat. Cancer Inst. 3: 555-558 (1943). 10. I}iPA0L0, J.A., and D0N{}VAX, P.J.: Properties of Syrian hamster cells transformed in the presence of carcinogenic hydrocarbons. uxp. Cell Res. 48: 361-377 (1967). 11. BORE'FREUh'D, E., KRIM, M., SANDERS, F. K. , STERBERG, S., and Bz:iJ ICH, A. : Malignant conversion of cells in vitro by carcinogens and viruses. Proc. Nat. Acad. Sci, U.S.A. 56: 672-679 (1966). 12. KURQKI, T., and SATO, H.: Transformation and neoplastic development r of hamster embryonic cells by 4-nitroquinoline-l-oxide and its derivatives. J. Nat. Cancer Inst 41: 53-71 (1968). 13. SAMERS, F.K., and BURFORD, B.O.: Morphological conversion of cells in vitro by N-nitrosomethylurea. Nature (London) 213: 1171-1173 (1967). 14. FREEXAN, A.E., KELLOFF, G.J., GILDEN, R.V., LA11tT, W.T., SWAIN, A.P., and H[7EB\ER, R.J.: Activation and isolation of hamster-specific C-type RNA viruses from tumors induced by cell cultures transformed by chemical carcinogens. Proc. Nat. Acad. Sci, U.S.A., In press. 15. SARMA, P.S., TURNER, H.C., and IiUEBXER, R.J.: An avian leukosis group-specific complement fixation reaction. Application for the detection and assay of non=cytopathogen.i.c leukosis viruses. Virology 23: 313-321 (1964). Ib. TYNDALL, R.L., TEETER, E., OTTEN, J.A., BOWLES, N.D., VIDRI:.y, J.G., UPTON, A.C., and WALBURG, H.E., Jr.: Further observations on in vitro cytopathic effects associated with murine leukemia virus infection. Int. J. Cancer 1: 565-572 (1966).
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17. IOACHIM, H.L.: Neoplastic transformation of rat thymic cells induced in vitro ss leukemia virus. Science 155: 585-587 (1967). 18. RHIM, J.S., Ht3EBNER, R.J., and TING, R.C.: Transformation of hamster embryo cells _ I1:=o ,7f Rauschar lei=sCc^:,a virus. J. :iai.. i.ar.c2.'. :ilsZ. 42: 1053-1060 (1969). 19. ItHIM, J.S., IRTEBI:.R, R.J., TING, R.C., kTVy.L, N., and VASS, GT.: Characteristics of a tumor cell line and virus derived from hamster tumors induced by Rauscher leukemia virus-transformed hamster embryo cells. Int. J. Cancer 5: 28-38 (1970). 20. RHI,i, J.S „ IiIIEg\EZ, R.J., LASE, W.T., and VEMN0N, M.L.: Neoplastic transformation of rat embryo cells induced in vitro by Rauscher leukemia virus. Proc. Soc. Exp. Biol. and Med. 133: 914-920 (1970). 21. RHIM, J.S., JOGZ.r KAR, M. H. , RICHARDSON, E.S., WIVEL, N.A., and =EB11.IER, R..T. : Long-term in vitro cultivation of Rauscher leukemia virus in rat embryo cells. Proc. Soc. Exp. Biol. and ::ed. 135: 160-166 (1970).

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