Epstein-Barrウイルス関連早期抗原発現誘導系による尿中膀胱発癌プロモーター検出の試み

Abstract

EBV潜在感染ヒトリンパ芽球様細胞(Raji細胞)のEBV関連早期抗原(EA)の発現誘導を指標とし, 膀胱発癌プロモーターの検出を試み, 既知の膀胱発癌物質8種, プロモーター5種, これらの投与をうけたラットの尿(Table 1), 膀胱癌42例の尿はすべてEBV-EA誘導活性を示さなかった

We assessed the possibility to detect promoters of bladder carcinogenesis by a short-term in vitro assay utilizing the activation of Epstein-Barr virus (EBV) expression in EBV genome-carrying human lymphoblastoid cells. This system is composed of EBV-nonproducer Raji cells as the indicator, n-butyrate as the EBV-inducer and the test substance. None of eight known bladder carcinogens (2-naphthylamine, 2-acetylaminofluorene, N-butyl-N-(4-hydroxybutyl)nitrosamine, N-butyl-N-(3-carboxypropyl) nitrosamine, N-methyl-N-nitrosourea, N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide, benzidine, cyclophosphamide) or five promoters (sodium saccharin, sodium cyclamate, urea, allopurinol, DL-tryptophan) were detected by this system. Normal urine from 20 rats did not activate the EBV genome. Neither the 0.45 micron membrane filtrates nor ether extracts of urine obtained from rats given one of 4 bladder carcinogens, 4 promoters or phorbol 12-myristate 13-acetate reacted with this system, whereas those from rats given either vincristine or vinblastine did, although their activity for promoting bladder carcinogenesis is not known. Urine samples from 42 patients with bladder cancers, when tested as filtrates, ether extracts or XAD-2 resin adsorbates, did not activate EBV expression. These results suggest that EBV-activating substances contribute little to promotion of bladder carcinogenesis and that this test might not be applicable for screening of tumor promoters in urine.