Mutagenicity of
            N
            ‐hydroxy‐4‐aminobiphenyl in human
            TP53
            knock‐in (Hupki) mouse embryo fibroblasts

The transforming potential and oncogenicity of a simian virus 40 (SV40) mutant affecting T-antigen (T-ag), SV40(cT)-3, was examined in an effort to dissect T-ag functions in transformation. SV40(cT)-3 has a point mutation at nucleotide 4434 that abolishes the transport of T-ag to the nucleus but does not affect its association with the cell surface. Transfection-transformation assays were performed with primary cells and established cell lines of mouse and rat origin. The efficiency of transformation for established cell lines by SV40(cT)-3 was comparable to that of wild-type SV40, indicating that transformation of established cell lines can occur in the absence of detectable amounts of nuclear T-ag. Transformation of primary mouse embryo fibroblasts by SV40(cT)-3 was markedly influenced by culture conditions; the relative transforming frequency was dramatically reduced in assays involving focus formation in low serum concentrations or anchorage-independent growth. Immunofluorescence tests revealed that the transformed mouse embryo fibroblasts partially transport the mutant cT-ag to the cell nucleus. Transformed cell lines induced by SV40(cT)-3 did not differ in growth properties from wild-type transformants. SV40(cT)-3 was completely defective for the transformation of primary baby rat kidney cells, a primary cell type unable to transport the mutant T-ag to the nucleus. The intracellular localization of cellular protein p53 was found to mimic T-ag distribution in all the transformants analyzed. The mutant virus was weakly oncogenic in vivo: the induction of tumors in newborn hamsters by SV40(cT)-3 was reduced in incidence and delayed in appearance in comparison to wild-type SV40. These observations suggest that cellular transformation is regulated by both nuclear and surface-associated forms of SV40 T-ag.

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Transplantation of Mouse Embryo Fibroblasts: An Approach to Study the Physiological Pathways Linking the Suprachiasmatic Nucleus and Peripheral Clocks

Methods in Enzymology - Circadian Rhythms ◽

10.1016/s0076-6879(05)93023-1 ◽

2005 ◽

pp. 469-478 ◽

Cited By ~ 4

Author(s):

Sehyung Cho ◽

Irene Yujnovsky ◽

Masao Doi ◽

Paolo Sassone-Corsi

Keyword(s):

Suprachiasmatic Nucleus ◽

Mouse Embryo ◽

Mouse Embryo Fibroblasts ◽

Peripheral Clocks ◽

Physiological Pathways ◽

Embryo Fibroblasts

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METABOLISM OF BENZO(A)PYRENE AND ONCOGENIC TRANSFORMATION OF C3H/10T1/2 MOUSE EMBRYO FIBROBLASTS

Microsomes, Drug Oxidations and Chemical Carcinogenesis ◽

10.1016/b978-0-12-187702-6.50086-4 ◽

1980 ◽

pp. 1013-1024 ◽

Cited By ~ 1

Author(s):

Charles Heidelberger ◽

E.B. Gehly ◽

W.E. Fahl ◽

Colin R. Jefcoate

Keyword(s):

Mouse Embryo ◽

Oncogenic Transformation ◽

Mouse Embryo Fibroblasts ◽

Embryo Fibroblasts

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Effect of Daunorubicin and Adriamycin on Nucleic ACID Synthesis of Serum Stimulated Mouse Embryo Fibroblasts

Tumori Journal ◽

10.1177/030089167706300105 ◽

1977 ◽

Vol 63 (1) ◽

pp. 31-41 ◽

Cited By ~ 11

Author(s):

Rosanna Supino ◽

Anna M. Casazza ◽

Aurelio Di Marco

Keyword(s):

Dna Synthesis ◽

Mouse Embryo ◽

Rna Synthesis ◽

Calf Serum ◽

Acid Synthesis ◽

Anthracycline Antibiotics ◽

Simple Method ◽

Mouse Embryo Fibroblasts ◽

Embryo Fibroblasts

This paper reports the effects of daunorubicin and adriamycin on DNA and RNA synthesis of in vitro cultured mouse embryo fibroblasts (MEF) stimulated by fetal calf serum (FCS). The addition of FCS to quiescent MEF cultures brings about a wave of RNA synthesis, followed by DNA synthesis which starts between 8 and 12 h after change of medium and proceed for up to 24 h. These cells are therefore partially synchronized. The level of DNA synthesis depends on the amount of FCS added. Daunorubicin and adriamycin are almost equally effective in inhibiting DNA synthesis, as well as cell proliferation, which takes place later. Adriamycin is more active than daunorubicin on RNA synthesis. In cultures treated for an 8 h period starting at different times after FCS addition, the highest DNA synthesis inhibition is achieved by treatment during the first 8 h, when DNA synthesis has not yet started. The cellular uptake of daunorubicin is constantly higher than that of adriamycin, in any experimental condition tested. The results show that FCS-stimulated MEF can provide a simple method for studying the effects of anthracycline antibiotics on partially synchronized cells.

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