My research focuses on the mechanisms of environmentally induced cellular lesions. Our emphasis is on the evaluation of the initial chemical, molecular, biochemical, and structural alterations in the cellular macromolecules following their interactions with environmental chemicals or their reactive metabolites. These interactions may lead to various chemically induced human diseases such as the far-delayed carcinogenesis.
Our working hypothesis implies that the metabolic bio-activation of environmental chemicals to reactive intermediates (RM) by various oxidative enzymes such as cytochrome P450 and other oxidases and peroxidases, play a key role in the mechanisms of pathogenicity and carcinogenicity of chemicals. These RM attack DNA as the target molecule in organs where genetic damage and cancer are observed. DNA damage may be induced by DNA adduct formation and incomplete DNA repair. Also the RM may induce oxidative stress in the cells by depleting the cellular reserves of the nucleophilic antioxidant tripeptide glutathione(GSH). Oxidative stress in the cells is reflected by the production of reactive oxygen species (ROS), such as superoxide anion, hydrogen peroxide, and hydroxyl radicals. ROS may be implicated in further damage of biologically important macromolecules such as DNA, lipids, and proteins. These interactions lead to the initiation of apoptosis; programmed cell death, mutagenic and possibly carcinogenic effects of environmental chemicals.
Ahmed, A.E., Jacob, S., Nouraldeen, A.M. Chloroacetonitrile (CAN) induces glutahione depletion and 8-Hydroxylation of guanine bases in gastric mucosal DNA of rats. J Biochem Toxicol 13(3), 1999.
Jacob, S., Abdel-Aziz, A.H., Shouman, S.A., Ahmed, A.E. Effect of glutathione modulation on the distribution and transplacental uptake of 2-[14C] chloroacetonitrole (CAN). Quantitative whole-body autoradiographic study in pregnant mice. Toxicol Indus Health 14(4):533-546, 1998.
Hamada, E.M., Abdel-Aziz, A.H., Abd-Allah, A.R., Ahmed, A.E. Possible functional immunotoxicity of acrylonitrile. Pharmacol Res 37(2):123-129, 1998.
Ahmed, A.M., Jacob, S., Giovanella, B.C., Kosielski, A.J., Liehr, J.G., Stehlin, J.S.-Jr. Comparative disposition of the antioneoplastic agent 9-nitro camptothecin and inactive isomer 12-nitro camptothecin in CASE-bearing nude mice: effect of route of administration on tissue distribution. Cancer Chemother Pharmacol 41:29-36, 1997.
Abdel-Aziz, A.H., Abdel-Naim, A.B., Hamada, F.M., Ahmed, A.E. In-vitro bioactivation of acrylonitrile. Pharmacological Res 35(2):129-134, 1997.
Muntaz, M.M., Farooqui, M.Y., Ahmed, A.E. Propioinitrile whole-body autoradiography, conventional toxicokinetics and metabolism studies in rats. Toxicol Industrial Health 13(1):27-41, 1997.