The impact of hypoxia on the activity of lactate dehydrogenase in two different pre-clinical tumour models.

OBJECTIVE

To investigate the direct relationship between tumour hypoxia and lactate dehydrogenase (Ldh) levels in serum and tumour in two different pre-clinical murine models.

METHODS

Experiments were performed in CDF1 or C3H/ Km mice implanted with a C3H mammary carcinoma and SCCVII squamous cell carcinoma, respectively. Low oxygen breathing for 1-72 h was used to increase tumour hypoxia. Ldh activity was measured in the serum and tumour cytosole with a colorimetric method. Tumour Ldha mRNA levels were assessed with RT-PCR. RESULTS; The serum Ldh in non-tumour bearing CDF1 mice and C3H/km mice was 10.592 U/ml and 1292 U/ml, respectively. For C3H mammary carcinoma bearing mice, a positive correlation between tumour volume and tumour and serum Ldh was found. Tumour Ldh in SCCVII carcinomas also increased with increasing tumour volume, but no volume dependence of serum Ldh was found. Low oxygen breathing caused a 2-3 fold increase in tumour Ldha mRNA in both tumour models. In C3H mammary carcinoma bearing mice, serum and tumour Ldh significantly increased after 48 and 72 hours of hypoxia, respectively. Low oxygen breathing did not change serum and tumour Ldh in SCCVII carcinoma bearing mice. Reoxygenation for 4 or 24 hours had no additional effect on Ldh activity in any of the models.

CONCLUSIONS

Serum Ldh activity can be a marker for tumour burden in certain types of cancer. The relationship between serum and tumour Ldh and tumour hypoxia has not been confirmed. However, Ldha mRNA may be a potential new marker of tumour hypoxia and should be further investigated.