Poly(ADP-ribose) polymerase-1 polymorphisms, expression and activity in selected human tumour cell lines

Background:

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA-binding enzyme activated by DNA breaks and involved in DNA repair and other cellular processes. Poly(ADP-ribose) polymerase activity can be higher in cancer than in adjacent normal tissue, but cancer predisposition is reported to be greater in individuals with a single-nucleotide polymorphism (SNP) V762A (T2444C) in the catalytic domain that reduces PARP-1 activity.

Methods:

To resolve these divergent observations, we determined PARP-1 polymorphisms, PARP-1 protein expression and activity in a panel of 19 solid and haematological, adult and paediatric human cancer cell lines.

Results:

There was a wide variation in PARP activity in the cell line panel (coefficient of variation, CV=103%), with the lowest and the highest activity being 2460 pmol PAR/10⁶ (HS-5 cells) and 85 750 pmol PAR/10⁶ (NGP cells). Lower variation (CV=32%) was observed in PARP-1 protein expression with the lowest expression being 2.0 ng μg⁻¹ (HS-5 cells) and the highest being 7.1 ng μg⁻¹ (ML-1 cells). The mean activity in the cancer cells was 45-fold higher than the mean activity in normal human lymphocytes and the PARP-1 protein levels were 23-fold higher.

Conclusions:

Surprisingly, there was no significant correlation between PARP activity and PARP-1 protein level or the investigated polymorphisms, T2444C and CA.