N-OH-AABP Modifications in Human DNA May Lead to Auto-Antibodies in Bladder Cancer Subjects.

Uzma Shahab,Qurain Turki Alshammari,Shafiul Haque,Moin Uddin,Safia Habib,Ahmad Alsulimani,Saheem Ahmad,Abdulrahman A Alatar

doi:10.3390/diagnostics12020337

Abstract

4-Aminobiphenyl (4-ABP) and other related arylamines have emerged to be responsible for human urinary bladder tumors and cancers. Hemoglobin-ABP adducts have been recognized in the blood of smokers, and it builds up in the circulatory system over the period of years that might lead to a bladder tumor. N-hydroxy-Acetyl 4-Aminobiphenyl (N-OH-AABP) is one of the reactive forms of 4-ABP which has a potential to initiate tumor growth and causes cancer rapidly. In the present study, commercially available human DNA was modified by N-OH-AABP, and its modifications were analyzed biophysically from fluorescence spectroscopy and thermal denaturation studies. Further, Sera and IgG from bladder cancer patients’ blood were assessed for affinity to native and N-OH-AABP modified human DNA using ELISA. The study showed N-OH-AABP caused damage in the structure of the DNA macromolecule and the perturbations resulting from damage leads to change in the Tm of the DNA molecule. Bladder cancer auto-antibodies, particularly in smoker group, showed preferential binding to N-OH-AABP modified human DNA. This study shows that N-OH-AABP modified DNA could be an antigenic stimulus for the generation of autoantibodies in the sera of bladder cancer patients.

Highlights

Aromatic amines are among the first chemical carcinogens that have been implicated in human cancers [1]
A decrease in the fluorescence intensity of the EtBr-N-OH-AABP-modified human DNA compared to EtBr-DNA in the fluorescence emission spectra confirms the destruction of structural integrity of DNA and generation of strand breaks, which result in poor intercalation of EtBr in the modified form of DNA [18]
The present study discusses the modification of human DNA brought about by a carcinogen, N-OH-AABP

Summary

Introduction

Aromatic amines are among the first chemical carcinogens that have been implicated in human cancers [1]. Ample evidence from both epidemiological studies and animal models has firmly established that arylamines, 4-aminobiphenyl (4-ABP), are the major culprits in bladder cancer related to occupational exposures [2]. It has been revealed to be a foremost etiological driving force of human bladder cancer, and to be a strong urinary bladder carcinogen in experimental animals. The aromatic amine 4-aminobiphenyl still continues to be an environmental and occupational contaminant, since it is generated mainly from cigarette smoke

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