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.
Lukacova
Slavka
S
Department of Experimental Clinical Oncology, Aarhus University Hospital, Noerrebrogade 44, DK-8000 Aarhus, Denmark. slavka@oncology.dk
Sørensen
Brita S
BS
Alsner
Jan
J
Overgaard
Jens
J
Horsman
Michael R
MR
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism*; D015687:Cell Hypoxia; D003600:Cytosol / Q000201:enzymology*; D004195:Disease Models, Animal; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D007770:L-Lactate Dehydrogenase