Temporal heterogeneity in oxygen tension in human melanoma xenografts - PubMed (original) (raw)

Temporal heterogeneity in oxygen tension in human melanoma xenografts

K G Brurberg et al. Br J Cancer. 2003.

Abstract

The spatial heterogeneity of the oxygen tension (pO(2)) in human and experimental tumours has been studied extensively, whereas studies of the temporal heterogeneity in pO(2) are sparse. In the work reported here, pO(2) was measured continuously over periods of at least 60 min in A-07 human melanoma xenografts by using the OxyLite fibre-optic oxygen-sensing device. The main purpose of the work was to establish the usefulness of the OxyLite system in measuring the temporal heterogeneity in pO(2) in tissues and to characterise the fluctuations in tissue pO(2) in A-07 tumours. The OxyLite device was found to be suitable for studies of the temporal heterogeneity in pO(2) in tumours. However, potential pitfalls were identified, and reliable pO(2) measurements require that precautions are taken to avoid these pitfalls, that is, erroneous pO(2) readings caused by tissue trauma induced by the probe, probe movements induced by reflex actions of the host mouse and occasional probe drift. Significant fluctuations in pO(2) were detected in the majority of the 70 tumour regions subjected to measurement. The fluctuations in different regions of the same tumour were in general temporally independent, implying that they were caused primarily by redistribution of the tumour perfusion rather than fluctuations in global perfusion. Fourier analysis of the pO(2) traces showed that the pO(2) usually fluctuated at frequencies lower than 1.5-2.0 mHz, corresponding to less than 0.1 cycle min(-1). Haemodynamic effects may cause pO(2) fluctuations in this frequency range, and hence, the redistribution of the perfusion could have been caused by morphological abnormalities of the tumour microvasculature. Moreover, acute hypoxia, that is, pO(2) fluctuations around 10 or 5 mmHg, was detected in 20 of 70 regions, that is, 29% (10 mmHg), or 27 of 70 regions, that is, 39% (5 mmHg). The median fraction of the time these regions were acutely hypoxic was 73% (10 mmHg) or 53% (5 mmHg). Consequently, if A-07 tumours are adequate models of tumours in man, acute hypoxia may be a commonly occurring phenomenon in neoplastic tissues, and hence, acute hypoxia is likely to cause resistance to radiation therapy and promote tumour aggressiveness.

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Figures

Figure 1

Figure 1

Examples of _p_O2 traces recorded with OxyLite probes in A-07 tumours (A) and muscle tissue (B). The traces show that the changes in _p_O2 were more pronounced shortly after the probe insertion than towards the end of the observation period.

Figure 2

Figure 2

Sum of 50 normalised _p_O2 traces recorded with OxyLite probes in A-07 tumours. The composed trace shows that the changes in _p_O2 recorded within the first 20 min after the probe insertion were systematic, whereas those recorded beyond the first 20 min were random.

Figure 3

Figure 3

Examples of _p_O2 traces recorded with OxyLite probes in A-07 tumours. The traces refer to tumour regions without significant fluctuations in _p_O2 (A) and tumour regions showing significant fluctuations in _p_O2 around _p_O2 values of 5 and 10 mmHg (B).

Figure 4

Figure 4

Examples of _p_O2 traces recorded simultaneously with OxyLite probes in two regions of the same A-07 tumours. The traces refer to a tumour where the _p_O2 values were correlated (A) and a tumour where the _p_O2 values were inversely correlated (B).

Figure 5

Figure 5

Example of a _p_O2 trace recorded with an OxyLite probe in an A-07 tumour (A) and the corresponding frequency spectrum (B). The frequency spectrum, which was obtained by subjecting the _p_O2 data to Fourier analysis, suggests that the _p_O2 fluctuated at frequencies lower than 1.5–2.0 mHz.

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