Circulating antibodies directed against "polycyclic aromatic hydrocarbon-like" structures in the sera of cancer patients.
BACKGROUND
An increase in immunoglobulin (Ig) A isotype directed against benzo(a)pyrene (BP) structure has previously been described in sera of cancer patients. In this study, new polycyclic aromatic hydrocarbon (PAH) conjugates were synthesized in order to more closely mimic the endogenous ligands of the cytosolic aryl hydrocarbon receptor (AhR). PAH [benzo(a)pyrene; 1,2-benzanthracene; dibenz[a,c]anthracene; 7,12-dimethylbenza[a]anthracene; benzo(ghi)perylene] were bound to protein carriers such as bovine serum albumin (BSA) via N-acetyl-cysteine (NAC).


METHODS
The levels of circulating antibodies (Abs) directed against PAH-NAC conjugates in the sera of cancer patients were evaluated using an Enzyme-Linked Immunosorbent Assay (ELISA) with these new conjugates. The avidity (IC(50)) and specificity of these circulating Abs were assessed via competition experiments.


RESULTS
An increase in Ig directed against these PAH-NAC conjugates was found in the sera of cancer patients, irrespective of the state and stage of the tumors. These Ig were principally of the A isotype. Sera from cancer patients had significantly higher optical density (OD) ranges than the controls, p<0.0001. The ELISA test for breast cancer (n=155) and ovarian cancer (n=62) identified 82% and 92% of positive patients, respectively. The percentage positive in the control group (n=60) was around 5%. Moreover, competition experiments with the different PAH-NAC conjugates and NAC-BSA revealed an estimated avidity of 10(-6)M for the circulating IgA antibodies.


CONCLUSIONS
The Abs discriminated between the different PAH-NAC conjugates and NAC-BSA. Therefore, these Abs recognize a carcinogenic PAH-NAC structure and not only a BP structure. These markers may be useful in the future for monitoring cancer evolution and recurrence.
Pouns
Olivier
O
Institut Pour le Développement de la Recherche en Pathologie Humaine et Thérapeutique (IDRPHT), Talence, France.
Mangas
Arturo
A
Coveñas
Rafael
R
Geffard
Michel
M
D000111:Acetylcysteine / Q000276:immunology* / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology*; D008024:Ligands; D008593:Menopause; D010051:Ovarian Neoplasms / Q000097:blood / Q000276:immunology*; D011084:Polycyclic Aromatic Hydrocarbons / Q000276:immunology* / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000276:immunology; D012710:Serum Albumin, Bovine
D000912:Antibodies, Neoplasm; D002352:Carrier Proteins; D007070:Immunoglobulin A; D007136:Immunoglobulins; D008024:Ligands; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D012710:Serum Albumin, Bovine; D000111:Acetylcysteine