INCREASED DEGRADATION OF ALBUMIN IN CANCER IS NOT DUE TO CONFORMATIONAL OR CHEMICAL MODIFICATIONS IN THE ALBUMIN MOLECULE

This study has evaluated whether increased albumin degradation in a tumor-bearing host is dependent on previously recognized chemical and environmental modifications in the albumin molecule as observed by others and ourselves. For the purpose, adult sarcoma-bearing mice with increased albumin degradation and electrophoretic heterogeneity were used and compared to freely fed (FF) or food restricted control animals. Food restricted control animals such as pair-fed (PF) and pair-weighed (PW) served to match the anorexia and malnutrition observed in tumor-bearing animals. The serum albumin concentration was decreased (P < 0.05) in tumor-bearing animals (33 ± 5 g/liter) compared to pair-fed (40 ± 3), pair-weighed (41 ± 4), and freely fed control mice (43 ± 3). Isoelectric focusing of plasma between pH 3 and 10 and pH 4 and 6.5 confirmed a different isoelectric point for albumin in tumor-bearing animals compared to control animals. Albumin degradation was 33% higher in tumor-bearing mice compared to freely fed controls (P < 0.01). Tumor-bearing animals had also significantly increased turnover of albumin compared to all control animals (0.13 ± 0.022 mg/hr/g animal vs 0.05 ± 0.008 mg/hr/g in PW; 0.08 ± 0.009 in PF, and 0.09 ± 0.007 in FF). The acidic fraction of albumin had a more rapid fractional turnover than the more basic components in both tumor-bearing and control animals. However, both the anodal and the cathodal albumin in tumor-bearing mice had a higher turnover compared with corresponding fractions of albumin from control animals. Endogenously or exogenously labeled albumin from tumor-bearing animals did not show any increased disappearance when transfused back into normal animals, while labeled albumin from normal and tumor-bearing animals showed a significantly higher disappearance when transfused into tumor-bearing animals. The results demonstrate that elevated albumin degradation and turnover in cancer disease is dependent on host factors that are not associated with the chemical heterogeneity of the albumin molecule itself generally seen in a tumor-bearing host. © 1990.