Chemical carcinogen Epstein-Barr virus (EBV) synergism: EBV genome amplification and site-specific mutation during transformation.

Abstract:

:When treated with chemical carcinogens, peripheral blood lymphocytes (PBLs) from normal adults or patients with acquired immunodeficiency syndrome (AIDS) were more readily transformed than non-treated PBLs into immortalized lymphoblastoid cell lines (LCLs) by the Epstein-Barr virus (EBV, FF41-1). Chemical carcinogens also enhanced spontaneous transformation in both PBL populations. Co-cultivation of lethally ultraviolet (UV)-irradiated uninfected PBLs with EBV-infected PBLs resulted in a dose-related enhancement of transformation, providing evidence that enhancement is in part mediated by carcinogen-induced diffusible trans-acting factors. Analysis of the EcoRI J region of resident EBV genomes showed that LCLs established from carcinogen-treated PBLs frequently had EBV genome amplification higher than that seen in controls. Carcinogen-induced EBV genome amplification was shown to be dose-related. The organization of the terminal region of the EBV genome was analyzed in LCLs derived from carcinogen-treated PBLs and compared to that of FF41-1 and B95-8. LCLs established from N-methyl-N'-nitroso-nitrosoguanidine (MNNG)- and aflatoxin B1-treated PBLs frequently had 2 circular forms of the EBV genome and several linear forms varying by numbers of terminal repeats (TRs) at the 3' and 5' end. This is in contrast to the single episomal circular and linear form of the EBV genome found in the parent FF41-1 and single episomal circular form in control FF41-1-carrying LCLs. Linear forms of the EBV genome were only found in FF41-1-transformed LCLs derived from carcinogen-treated PBLs and were associated with the production of unusually large amounts of infectious EBV. These results demonstrate that chemical carcinogen-mediated enhancement of transformation is accompanied by quantitative and qualitative alterations in the physical structure, organization and expression of the EBV genome which may in turn be the result of a carcinogen-induced cellular SOS response.

journal_name

Int J Cancer

authors

Henderson EE,Franks C,Fronko G

doi

10.1002/ijc.2910430116

subject

Has Abstract

pub_date

1989-01-15 00:00:00

pages

72-9

issue

1

eissn

0020-7136

issn

1097-0215

journal_volume

43

pub_type

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