title: N-acetyl-L-cysteine simultaneously increases mitogenesis and suppresses apoptosis in mitogen-stimulated B-lymphocytes from p53 haploinsufficient Tg.AC (v-Ha-ras) mice.
abstract: Recent epidemiological evidence suggests that antioxidants may enhance carcinogenesis by promoting cellular proliferation and/or impeding programmed cell death. We examined the effect of N-acetyl-l-cysteine (NAC) on mitogenesis and apoptosis in splenocytes from p53 haploinsufficient Tg.AC (v-Ha-ras) mice. This model contains genetic lesions found frequently in human cancer and is predisposed to develop carcinogen-induced cancer. Splenocytes were incubated with NAC alone or with the B- and T-cell-specific mitogens Concanavalin A (Con A) and E. coli lipopolysaccharide (LPS), respectively. Mitogenesis increased 17-fold in mitogen-stimulated cultures and 10-fold in cultures incubated with NAC alone. Co-incubation with both NAC (1000 microg/mL) and mitogen increased mitogenesis by 33-fold without changing apoptosis rates. Strikingly, incubation with NAC and LPS attenuated LPS-induced apoptosis. Mitogen alone did not affect GSH levels but NAC-induced increases were significantly depleted by co-incubation with mitogen. Furthermore, NAC increased the number of CD45R+ B cells, but decreased CD3+ T cells showing enhanced survival of B cells under these conditions. These results demonstrate concurrent reduced apoptosis and increased mitogenesis in B lymphocytes that may favor clonal selection of preneoplastic cells.
authors.affiliation: Transgenic Carcinogenesis Unit, Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Services, NIH, Research Triangle Park, North Carolina 27709, USA. martin9@niehs.nih.gov
authors.forename: K R
authors.initials: KR
authors.lastname: Martin
authors.forename: F W
authors.initials: FW
authors.lastname: Kari
authors.forename: J C
authors.initials: JC
authors.lastname: Barrett
authors.forename: J E
authors.initials: JE
authors.lastname: French
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D005978:Glutathione / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects* / Q000276:immunology; D015689:Oncogene Protein p21(ras) / Q000235:genetics; D010084:Oxidation-Reduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D008934:Mitogens; D016159:Tumor Suppressor Protein p53; D003208:Concanavalin A; D015689:Oncogene Protein p21(ras); D005978:Glutathione; D000111:Acetylcysteine