FURTHER EVALUATION OF NICOTINAMIDE AND CARBOGEN AS A STRATEGY TO REOXYGENATE HYPOXIC CELLS IN-VIVO - IMPORTANCE OF NICOTINAMIDE DOSE AND PREIRRADATION BREATHING TIME
Dj. Chaplin et al., FURTHER EVALUATION OF NICOTINAMIDE AND CARBOGEN AS A STRATEGY TO REOXYGENATE HYPOXIC CELLS IN-VIVO - IMPORTANCE OF NICOTINAMIDE DOSE AND PREIRRADATION BREATHING TIME, British Journal of Cancer, 68(2), 1993, pp. 269-273
The combination of nicotinamide and carbogen breathing is awaiting cli
nical evaluation as a strategy to overcome tumour hypoxia and thus enh
ance radiation response. We have continued our evaluation of this appr
oach in the murine SCCVII tumour with the aim of determining the impor
tance of nicotinamide dose and the pre-irradiation breathing time (PIB
T) for carbogen. For carbogen breathing alone maximal enhancement of r
adiation response was observed with PIBT's of between 5 and 30 min. Wh
en nicotinamide (1,000 mg kg-1 IP) was administered 60 min prior to ir
radiation little or no variation in radiation response was observed fo
r all the PIBT's examined (5-90 min). Indeed at all PIBT's the cell su
rvival obtained for the carbogen nicotinamide and radiation combinatio
n was indistinguishable from that expected for a fully aerobic respons
e. For PIBT's of 15 and 60 min we examined the influence of nicotinami
de doses between 50 and 1,000 mg kg-1. Significant radiosensitising ef
fects were observed for all nicotinamide doses tested above 50 mg kg-1
. Moreover for doses of 250 mg kg-1 and above the cell survival data w
as consistent with that expected for a fully aerobic response. No addi
tional benefit accrued from raising the nicotinamide dose above 250 mg
kg-1. These results indicate that significant radiosensitisation may
be expected even with clinically achievable nicotinamide doses when it
is combined with carbogen breathing. Furthermore, the use of nicotina
mide may reduce the critical importance of PIBT on the radiosensitisat
ion observed with carbogen.