Premium
Chemical carcinogen epstein‐barr virus (ebv) synergism: Ebv genome amplification and site‐specific mutation during transformation
Author(s) -
Henderson Earl E.,
Franks Carol,
Fronko Gerald
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910430116
Subject(s) - carcinogen , epstein–barr virus , biology , genome , virus , virology , malignant transformation , microbiology and biotechnology , genetics , gene
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‐I). 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 EcoR1 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 FF4I‐1 and B95‐8. LCLs established from N‐methyl‐N′‐nitroso‐nitrosoguanidine (NNNG)‐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.