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Examination of numerous sera from patients with infectious mononucleodis ( I M ) , Burkitt 's lymphoma ( B L ) or nasopharyngeal carcinoma ( N P C ) for antibodieh to Epstein-Barr virus ( E B V ) induced early antigens ( E A ) revealed two distinct patterns of immunofluorescence in abortively E B V-infected Raji cells. One showed diguse ( D ) staining of the nucleus and cytoplasm of invaded cells, the other ( R ) was restricted to masses in the cytoplasm. Although D-or R-reactive Raji cells became detectable at similar times after exposure to EBV, the percentages of D-positive cells initially exceeded R-positive cells but ultimately both were nearly equal in number. R-positive cells almost invariably contained also D. In EBV-exposed R P M l 64-10 cells, frequently only D was synthesized. D antigen, in contrast to R , resisted fixation by methanol or cthanol, whereas R proved more resistant than D to proteolytic enzymes. Comparative serum titration on acetone, respectively ethanol-fixed Ruji-EBV cell smears revealed that the transitory anti-EA response observed in many I

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Human B cell lymphoma and murine T cell leukemia can be initiated by several agents. The present paper formulates some thoughts on the role of cytogenetic changes in the subsequent neoplastic process. Initiation creates long-lived preneoplastic cells. In some respects, they are comparable to in vitro-transformed ("immortalized") cell lines that maintain a diploid karyotype and are not tumorigenic in vivo. The development of a tumorigenic ("autonomous") clone is dependent on additional changes at the genetic level. In human B and murine T cell Iymphoma, there are characteristic nonrandom chromosomal changes. The 14q+ marker appears to play a key role in human B cell lymphomas. The reciprocal 8;14 translocation in Burkitt lymphoma is a specialized subclass within this category. In murine T cell leukemia, trisomy 15 is the predominant change. The clustering of these nonrandom changes to tumors derived from a certain cell type rather than to tumors induced by a given etiological agent has important implications for the understanding of the genetic control of cellular responsiveness to growth-regulating forces in vivo.

Five peptides corresponding to amino acid sequences predicted from all three reading frames of the nucleotide sequence of the third internal repeat array (IR3) of the Epstein-Barr virus (EBV) genome were synthesized chemically. All five peptides elicited antipeptide antibodies in rabbits. The antiserum raised against a 14-residue copolymer of glycine and alanine gave brilliant EBV-specific nuclear staining in the anticomplement immunofluorescence (ACIF) Epstein-Barr virus (EBV) converts normal B lymphocytes into immortalized lymphoblastoid cell lines (1, 2). Conversion is regularly accompanied by the appearance of the EBV-determined nuclear antigen (EBNA) (3). EBNA has been detected in all EBV-genome-carrying cells by anticomplement immunofluorescence (ACIF) (4), including the two EBV-carrying human tumors, Burkitt lymphoma and nasopharyngeal carcinoma (5, 6). EBNA appears at a very early state of the primary transforming interaction between the virus and the B lymphocytes already before the onset of cellular DNA replication (7). In mitotic cells EBNA remains associated with the metaphase chromosomes (4), in contrast to the papovavirus T antigens that spread to the cytoplasm. This is in line with the strong DNA-binding properties of EBNA (8).The biochemical properties of EBNA have been studied in several laboratories. Proteins of various size classes varying from 200 to 48 kDa have been shown to react with human anti-EBNA-positive antisera (9-12). Strnad et al. showed that extracts of proteins of molecular size between 63 and 67 kDa were capable of inhibiting the ACIF reaction, and a correlation with an EBV-specific antigen varying in size between different EBV-carrying cell lines was suggested (12). Recent transfection studies with EBV DNA fragments have indicated that a nuclear antigen can be induced by BamHI K fragment (13). The BamHI K fragment contains the third internal repeat region (IR3). It consists of repeated hexa-or nonanucleotide sequences of only three nucleotide triplets: GGG, GCA, and GGA (14). Multiple homologous sequences are present on the human chromosomes, suggesting that the virus may originally have picked up this sequence from the host cell genome (15).Different isolates of EBV contain IR3 sequences of varying length (14). The length of the IR3 sequence is directly correlated with the size of an EBV-associated nuclear antigen varying in size between 68 and 85 kDa (16).The reading frame for transcription of this protein has recently been determined by immunizing rabbits with fusion proteins made in bacteria carrying plasmid clones containing P-galactosidase and IR3, joined in all three reading frames. The protein corresponding to reading frame 2 induced antibodies in rabbits that reacted with the IR3-related proteins on immunoblotting (17). However, EBNA reactivity of these antibodies was not proven by an ACIF reaction.If the IR3 region codes for EBNA or one of its major components, it should be possible to induce EBNA-specific, ACIF-reactive antibodies, by immunizing rabbits wit...

We have examined 17 primary undifferentiated nasopharyngeal carcinoma biopsies for allelic loss on 3p, comparing the findings in tumors with those in normal lymphocyte DNA from the same patients. Ten polymorphic microsatellite markers were used between 3p13 and 3p26. Allelic loss was observed in 12 samples (70%). Two loci were most frequently affected: D3S1067 (3p21.1-14.3) in 60% and D3S1217 (3p14.2-14.1) in 58%. One tumor seemed to have a homozygous deletion at 3p26, detected by the D3S1297 marker. Analysis of the clinical data showed that an increased number of aberrations in 3p was correlated with more advanced tumor stages.