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  • Title: Evaluation of the potential of hexamethylenetetramine, compared with tirapazamine, as a combined agent with {gamma}-irradiation and cisplatin treatment in vivo.
    Author: Masunaga S, Tano K, Watanabe M, Kashino G, Suzuki M, Kinashi Y, Ono K, Nakamura J.
    Journal: Br J Radiol; 2009 May; 82(977):392-400. PubMed ID: 19153181.
    Abstract:
    The purpose of this investigation was to compare the effect on intratumour quiescent (Q) cells in vivo of hexamethylenetetramine (HMTA) or tirapazamine (TPZ) in combination with gamma-irradiation and cisplatin treatment. Squamous cell carcinoma (SCC) VII tumour-bearing mice were administered 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumour proliferating (P) cells. The mice then received HMTA or TPZ intraperitoneally or continuously with or without gamma-irradiation or cisplatin treatment. Other tumour-bearing mice received HMTA or TPZ intraperitoneally immediately after gamma-irradiation. Immediately after gamma-irradiation or cisplatin treatment following HMTA or TPZ, or 24 h after gamma-irradiation followed by HMTA or TPZ, the response of Q cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of all tumour cells (P + Q) was determined from the BrdU-non-treated tumours. HMTA was more toxic to the subset of Q cells than to the population of tumour cells as a whole, similar to the findings for TPZ. The radiosensitising effect of HMTA was similar to that of TPZ in both all cells and Q cells. The recovery-inhibiting effect of HMTA was reliable, but not as great as that of TPZ. The cisplatin sensitivity-enhancing effect of HMTA was similar to or slightly greater than that of TPZ. Continuous administration of both HMTA and TPZ resulted in higher radiosensitivity- and cisplatin sensitivity-enhancing effects than did a single i.p. administration. We concluded that, in terms of the total tumour cell killing effect, including killing of Q cells, gamma-irradiation and cisplatin treatment combined with continuous HMTA administration is a promising strategy given that HMTA is used in clinics.
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