The feasibility of using adenovirus 5 as an in vitro probe for chemosensitivity in short-term cultures of human
tumors was evaluated using human
melanoma cell lines and primary cultures of
melanoma biopsies. A convenient immunoperoxidase method was developed for quantitating viral replication 2 days after
infection. Two different approaches were explored: the host cell reactivation assay (HCR) using
drug-treated virus; and the viral capacity assay using
drug-treated cells. The HCR assay detected sensitivity to
5-(3-methyl-1-triazeno)imidazole-4-carboxamide (
MTIC) in Mer- (methyl excision repair deficient) cell lines as decreased ability of the cells to replicate
MTIC-treated virus. This test should be applicable to
DNA-damaging agents and repair-deficient
tumors. Adenovirus replicated readily in nonproliferating primary cultures of
melanoma biopsies; application of the HCR assays to this material identified one Mer- sample of 11 tested. Herpes viruses were not suitable for use in HCR because herpes simplex virus type 1 failed to distinguish Mer- from Mer+
melanoma cells; and nonproductive
infection of
MTIC-sensitive lymphoid cells with Epstein-Barr virus yielded an
MTIC-resistant cell line. The second assay (viral capacity) involved determination of the inhibition of replication of untreated virus in treated cells. This approach correctly predicted sensitivity to
hydroxyurea and
deoxyadenosine in
melanoma cell lines when compared with clonogenic survival assay. Viral capacity was also inhibited by
cytosine arabinoside,
fluorouracil,
vincristine,
adriamycin,
6-mercaptopurine and ionising radiation, and may therefore be useful for detecting sensitivity to a wide range of
antitumor agents.