Do highly oncogenic group A human adenoviruses cause human cancer? Analysis of human tumors for adenovirus 12 transforming DNA sequences.

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Abstract
Adenovirus 12(Ad12)(Huie)(highly oncogenic group A) readily induces tumors in newborn rodents. Since Ad12 is isolated from human fecal samples, whether it plays a role in the etiology of human gastrointestinal cancer was investigated. If Ad12 is a causal agent of human cancer agent of human cancer, then human tumors should contain Ad12 transforming genes, as indicated by studies of cells transformed in vitro and in vivo by oncogenic viruses. Ad12 DNA and the Ad12 transforming restriction fragment (EcoRI-C fragment, left 16% of the viral genome) were labeled in vitro to 107 to 4 .times. 108 cpm/.mu.g by the nick translation reaction of DNA polymerase of Escherichia coli. The fidelity and sensitivity of these probes were established by analysis of DNA from Ad12-transformed cells and from hamsters with tumors induced by Ad12, reconstruction experiments with added Ad12 DNA and EcoRI restriction fragments, and comparison of annealing characteristics with Ad12 probes labeled in vivo. With Ad12[3H]DNA as probe, no viral DNA sequences were detected in 18 normal gastrointestinal tissues and 34 gastrointestinal tumors, including cancers of the colon, rectum, small intestine and stomach, under conditions that would detect 0.1 copy of the Ad12 genome/tumor cell. Similar analyses of Ad12-transformed hamster cells and Ad12 primary hamster tumors indicated 6-18 copies/cell of over 90% of the viral genome. With the Ad12 EcoRI-C transforming fragment as probe, no hybridization was detected with 32 human gastrointestinal tumors and 5 normal tissues; this result excludes 1-2% of the Ad12 genome/tumor cell. The data are strong evidence that Ad12 is not a major cause of human gastrointestinal cancer. The Ad12 transforming EcoRI-C fragment hybridized (50-68% efficiency) with other Ad12 isolates and with Ad18 and 31 (members of oncognic group A), but not at all with 28 other human Ad serotype. Other group A members probably are also not involved in human gastrointestinal cancer. No viral DNA sequences were detected in 12 normal lungs and 22 lung tumors, suggesting that respiratory cancer does not involve in Ad12 etiology.