Combined effect of para-aminobenzoic acid (PABA) and ionizing radiation in a syngeneic murine model of breast carcinoma

Abstract

3189 Background: PABA or p-amino benzoic acid is a water-soluble natural compound and a component of Vitamin B-12, thought to play a role in nucleotide base synthesis. It is widely available as a dietary supplement and is a common component of sunscreens. Previously, we observed that PABA enhanced the effects of radiation in B16F10 and G361 melanoma and Lewis Lung carcinoma in vitro, as well as in 4T1 breast carcinoma and B16F10 melanoma in a chick CAM in vivo model (ACR-NCI-EORTC, Nov. 2003). To further explore the role of PABA pre-clinically, we studied its effects as a radiosensitizer in the 4T1 syngeneic murine model of mammary carcinoma (Fred Miller, The Michigan Cancer Center). Methods: 4T1 tumor cells (5 x 104) were injected subcutaneously into the flank of BALB/C mice. Three days later, 28 mice were randomly assigned to PABA, administered daily for the duration of the experiment (1 mg/day), or no PABA treatment. At 14 days post-implantation, a randomization to radiation treatment (RT) occurred in both the PABA and non-PABA treated groups. A 60Co source was used to deliver a single fraction of 10 Gy to the tumor. Tumors were measured and volumes were calculated weekly for 28 days ((L2xW)/2). Results: At day 28, PABA injection alone had minimal effect on tumor growth (P=0.14); 10 Gy of ionizing radiation therapy significantly inhibited tumor growth by 47% (P=0.019); and PABA+10 Gy RT significantly inhibited tumor growth by 83% (P=0.000217) as compared to untreated controls. In addition, PABA+10 Gy RT resulted in a 68% inhibition of tumor growth as compared to radiation alone (P=0.00036). Conclusions: The most effective inhibition of tumor growth was achieved by PABA+10 Gy RT, suggesting that PABA is a radiosensitizer in this model. Given the high tolerability of PABA, these data may have significant translational potential. No significant financial relationships to disclose.