Potent inhibition of cell proliferation in the hippocampal dentate gyrus of mice by the chemotherapeutic drug thioTEPA.
Antimitotic drugs used in the chemotherapeutic treatment of cancers induce undesirable but unavoidable side-effects from interruption of normal mitotic processes throughout the body. We have examined whether several such drugs capable of penetrating the blood-brain barrier - thioTEPA and 5-fluorouracil - influence the normal process of cell proliferation underlying neurogenesis in the dentate gyrus of the hippocampus of mice. thioTEPA was found to yield a pronounced dose-related inhibition in cell proliferation, while 5-fluorouracil did not. The magnitude of the inhibition paired with a lack of observable impairment of health in mice indicates a suitable experimental model for elucidating the contributions of hippocampal cell proliferation to cognition and behavior.
Mignone
Robert G
RG
Department of Biochemistry, Rider University, Lawrenceville, NJ 08648 USA.
Weber
E Todd
ET
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000009:adverse effects; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013852:Thiotepa / Q000009:adverse effects*
D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D013852:Thiotepa; D005472:Fluorouracil