PMID- 9737426 OWN - NLM STAT- MEDLINE DCOM- 19981002 LR - 20211203 IS - 0278-6915 (Print) IS - 0278-6915 (Linking) VI - 36 IP - 9-10 DP - 1998 Sep-Oct TI - Characterization of cell-cycle arrest by fumonisin B1 in CV-1 cells. PG - 791-804 AB - Fusarium moniliforme is a widespread fungal pathogen which primarily infects corn, but can also infect rice or wheat. Fusarium moniliforme produce several mycotoxins, the most prominent of which is called fumonisin B1 (FB1). Epidemiological studies have indicated that ingestion of fumonisins correlates with a higher incidence of oesophageal cancer in Africa and China. Fumonisins also cause a neurodegenerative disease in horses, induce hepatic cancer in rats, are nephrotoxic in rats, or cause pulmonary oedema in swine. Structurally, fumonisins resemble sphingolipids and can alter sphingolipid biosynthesis. suggesting that sphingolipid alterations play a role in disease and carcinogenesis. Previous studies determined that FB1 blocked cell-cycle progression in CV-1 cells but not COS-7 cells. Herein, we have examined the effects that FB1 treatment has on cell-cycle regulatory proteins. Our studies established that FB1 treatment of CV-1 cells, but not COS-7 cells, leads to dephosphorylation of the retinoblastoma (Rb) protein. Cyclin dependent kinase 2 (CDK2) activity was repressed five- to 10-fold and cyclin E protein levels were lower in CV-1 cells after fumonisin treatment. Two CDK inhibitors, Kip1 and Kip2, were induced within 3 hours after fumonisin treatment of CV-1 cells, suggesting these two proteins mediate cell-cycle arrest induced by FB1. This mycotoxin caused large increases in sphinganine within 3 hours after addition of FB1. As sphingoid bases are known to induce Rb phosphorylation, this increase in sphinganinie might be the stimulus for the suppression of cyclin dependent kinase activities via Kip1 and Kip2. The ability of FB1 to accumulate sphingosine or sphinganine and arrest the cell cycle in some cells but not others may play an important role in carcinogenesis or disease. FAU - Ciacci-Zanella, J R AU - Ciacci-Zanella JR AD - Center for Biotechnology, Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln 68583, USA. FAU - Merrill, A H Jr AU - Merrill AH Jr FAU - Wang, E AU - Wang E FAU - Jones, C AU - Jones C LA - eng GR - GM46368/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Food Chem Toxicol JT - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JID - 8207483 RN - 0 (Carboxylic Acids) RN - 0 (Carcinogens, Environmental) RN - 0 (Cyclin E) RN - 0 (Enzyme Inhibitors) RN - 0 (Fumonisins) RN - 0 (Retinoblastoma Protein) RN - 0 (Tumor Suppressor Protein p53) RN - 3ZZM97XZ32 (fumonisin B1) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.22 (CDC2-CDC28 Kinases) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 2) RN - EC 2.7.11.22 (Cyclin-Dependent Kinases) RN - NGZ37HRE42 (Sphingosine) RN - OWA98U788S (safingol) SB - IM MH - Animals MH - Blotting, Western MH - *CDC2-CDC28 Kinases MH - COS Cells MH - Carboxylic Acids/*toxicity MH - Carcinogens, Environmental/*toxicity MH - Cell Cycle/*drug effects MH - Cell Line MH - Chlorocebus aethiops MH - Cyclin E/analysis MH - Cyclin-Dependent Kinase 2 MH - Cyclin-Dependent Kinases/analysis/antagonists & inhibitors MH - Enzyme Inhibitors/toxicity MH - *Fumonisins MH - Protein Serine-Threonine Kinases/analysis/antagonists & inhibitors MH - Retinoblastoma Protein/analysis MH - Sphingosine/analogs & derivatives/analysis MH - Tumor Suppressor Protein p53/analysis EDAT- 1998/09/16 02:04 MHDA- 2001/03/28 10:01 CRDT- 1998/09/16 02:04 PHST- 1998/09/16 02:04 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1998/09/16 02:04 [entrez] AID - S0278-6915(98)00034-9 [pii] AID - 10.1016/s0278-6915(98)00034-9 [doi] PST - ppublish SO - Food Chem Toxicol. 1998 Sep-Oct;36(9-10):791-804. doi: 10.1016/s0278-6915(98)00034-9.