The usefulness of
hexamethylenetetramine as an adjuvant to radiation and
cisplatin in the treatment of solid
tumors and its dependency on the p53 status of
tumor cells were examined. Human
head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a control (SAS/neo), were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The
tumor-bearing mice received
5-bromo-2'-deoxyuridine (
BrdU) continuously to label all proliferating (P) cells in the
tumors. Then, they received
hexamethylenetetramine (HMTA), intraperitoneally or continuously, combined with or without gamma-ray irradiation or
cisplatin treatment. Immediately
after treatment following HMTA, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for
BrdU. The response of the total (= P + Q)
tumor cells was determined from the
BrdU non-treated
tumors. A higher toxicity of HMTA to Q cells than total cells, especially in SAS/neo, was made less clear by continuous administration. There was no apparent difference in the radio- and
cisplatin-sensitivity enhancing effects by HMTA combination between SAS/neo and SAS/mp53
tumors, with a slightly greater effect in SAS/mp53. In both SAS/neo and SAS/mp53
tumors, continuous HMTA administration produced higher radio- and
cisplatin-sensitivity enhancing effects than intraperitoneal single administration. Therefore, the use of HMTA as an adjuvant to radiation or
cisplatin might be promising in curing solid
tumors with large fraction of hypoxic cells and also with frequent loss-of-function in p53.