Linked Life Data

11516527

Source:http://linkedlifedata.com/resource/pubmed/id/11516527

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2001-8-22
pubmed:abstractText
In vitro two-stage transformation, an important method for the screening of carcinogens, is a valuable approach for the mechanistic study of multi-stage carcinogenesis. However, very little is known about the molecular and cellular mechanisms, particularly in terms of cell cycle control during in vitro two-stage transformation. We improved the in vitro two-stage transformation method using N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as an initiator and cadmium as a promoter, and reconfirmed the promotional effect of cadmium (Fang et al., 2001a). To determine the alterations of cell cycle control in the MNNG-induced initiation stage during transformation, we examined the effects of MNNG on Balb/3T3 A31 cell growth, and determined the alterations of the protein and/or mRNA levels of cyclins B1, D1, E, and G, PCNA, GADD45, p27, and wild-type p53. After 4 hour treatment of MNNG, populations of G2/M phase distribution and apoptotic fraction and the cyclin G mRNA level increased, while the cyclin B1 mRNA level decreased in a concentration-dependent manner. Wild-type p53, p27, and GADD45 protein levels also increased as a function of MNNG concentrations. However, cyclin D1, cyclin E, and PCNA expressions remained unchanged. During the initiation stage, PCNA protein expression decreased on the first day after MNNG-treatment, then increased gradually during the following 6 days, and further increased on the first day after cadmium treatment. Although wild-type p53 and p27 protein expressions also showed temporary retardation on the first day after MNNG-treatment, the expressions increased gradually during the following 6 days, but decreased rapidly by the cadmium treatment. These results indicated that during the initiation stage, MNNG induced G2/M arrest and apoptosis with increased expressions of wild-type p53, p27, and GADD45 proteins; and down-regulated mRNA level of cyclin B1 and up-regulated mRNA level of cyclin G. In addition, although a few of the G2/M-arrested cells proliferated gradually, most cells continued to be suppressed and inactivated by the over-expressions of wild-type p53 and p27 until the cadmium treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-84
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11516527-3T3 Cells, pubmed-meshheading:11516527-Animals, pubmed-meshheading:11516527-Apoptosis, pubmed-meshheading:11516527-Carcinogens, pubmed-meshheading:11516527-Cell Cycle, pubmed-meshheading:11516527-Cell Transformation, Neoplastic, pubmed-meshheading:11516527-Cyclins, pubmed-meshheading:11516527-Flow Cytometry, pubmed-meshheading:11516527-G2 Phase, pubmed-meshheading:11516527-Methylnitronitrosoguanidine, pubmed-meshheading:11516527-Mice, pubmed-meshheading:11516527-Mice, Inbred BALB C, pubmed-meshheading:11516527-Microfilament Proteins, pubmed-meshheading:11516527-Mitosis, pubmed-meshheading:11516527-Muscle Proteins, pubmed-meshheading:11516527-Proliferating Cell Nuclear Antigen, pubmed-meshheading:11516527-RNA, Messenger, pubmed-meshheading:11516527-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11516527-Tumor Suppressor Protein p53
pubmed:year
2001
pubmed:articleTitle
Cell cycle was disturbed in the MNNG-induced initiation stage during in vitro two-stage transformation of Balb/3T3 cells.
pubmed:affiliation
School of Agricultural Biotechnology, Seoul National University, Suwon 441-744, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't