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4-Aminobiphenyl, a known carcinogen, has many environmental sources like cigarette smoke, industrial waste, and so forth. It can be metabolized to form a potent mutagen, N-hydroxy- N-acetyl-4-aminobiphenyl ( N-OH-AABP) that undergoes further processing to form electrophilic nitrenium ions which interact with DNA-forming covalent adducts, thereby exerting genotoxic effects. While the mutagenicity of N-OH-AABP has been amply reported, no extensive studies have been performed to assess the immunogenicity of N-OH-AABP-modified DNA. In this study, human placental DNA was modified with N-OH-AABP, and the structural perturbations in the DNA molecule were evaluated by ultraviolet spectroscopy and nuclease S1 digestion. Native and N-OH-AABP-modified DNA were used as antigens for immunizing female rabbits. The modified DNA was found to be highly immunogenic, eliciting high titer immunogen-specific antibodies, while the native form was almost nonimmunogenic. The induced antibodies exhibited wide range of heterogeneity in recognizing various nucleic acid conformers and DNA bases. We also detected deposits of immune complex in glomerular basement membrane in rabbits immunized with N-OH-AABP-DNA. Possible role of N-OH-AABP-DNA in the induction of antibodies in cancer patients and the related consequences have been discussed. © 2012 IUBMB Life, 64(4): 340-345, 2012 [ABSTRACT FROM AUTHOR]

A 5-year randomized, double blind, placebo-controlled study was carried out to determine the effect of the angiotensin-converting enzyme (ACE) inhibitor enalapril (E) on the progress of renal function and histology in subjects with type 1 diabetes and microalbuminuria. Seventy three type 1 diabetic patients with BP <140/90 and with persistent albuminuria (AER 20–200 μg/min) and normal renal function were randomly assigned to receive E (n=37) or placebo (n=36). A percutaneous renal biopsy was successfully performed in 69 patients and repeated in 59 patients after 5 years. The mean glomerular volume (MGV), mesangial volume (Vv mes) and glomerular basement membrane thickness (GBMT) were measured histomorphometrically. Before treatment, both groups had similar clinical characteristics, blood pressure, HbA1c, albumin excretion rate (AER), glomerular filtration rate (GFR), serum creatinine and renal structural damage. Blood pressure was well controlled in both groups. In the patients treated with E, albuminuria decreased significantly (P<0.05) and only 8.1% (3/37) of subjects progressed to clinical albuminuria (AER >300 mg/24 h) compared with 30.5% (11/36) in the placebo group. The E treatment resulted in absolute risk reduction of 22.4 percentage points for the development of clinical albuminuria over a 5-year period (P<0.01). After 5 years of treatment, GBM thickness showed a consistent, though statistically insignificant, increase in the placebo group, whereas it remained stable in the E group. A significant increase in MGV and Vv mes was also observed in the placebo group on completion of the study. The present study indicates that long term therapy with E may decrease or delay the progression of structural glomerular damage in microalbuminuric diabetic subjects without marked hypertension (BP <140/90). [Copyright &y& Elsevier]