Arsenite promotes centrosome abnormalities under a p53 compromised status induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

Journal Article · Mon Feb 15 04:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.11.012· OSTI ID:21344865

Liao, W -T ^[1]; Yu, H -S ^[2]

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1. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan (China)
2. Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China)

Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus an interaction between arsenite and cigarette smoking in lung carcinogenesis was suspected. In the present study, we investigated the interactions of a tobacco-specific carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (nicotine-derived nitrosamine ketone, NNK) and arsenite on lung cell transformation. BEAS-2B, an immortalized human lung epithelial cell line, was selected to test the centrosomal abnormalities and colony formation by NNK and arsenite. We found that NNK, alone, could enhance BEAS-2B cell growth at 1-5 muM. Under NNK exposure, arsenite was able to increase centrosomal abnormality as compared with NNK or arsenite treatment alone. NNK treatment could also reduce arsenite-induced G2/M cell cycle arrest and apoptosis, these cellular effects were found to be correlated with p53 dysfunction. Increased anchorage-independent growth (colony formation) of BEAS-2B cells cotreated with NNK and arsenite was also observed in soft agar. Our present investigation demonstrated that NNK could provide a p53 compromised status. Arsenite would act specifically on this p53 compromised status to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenite under tobacco-specific carcinogen co-exposure.

• OSTI ID: 21344865
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 243; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALKALOIDS
AMINES
ANIMAL CELLS
ANIMALS
APOPTOSIS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
AZOLES
BODY
CARCINOGENESIS
CARCINOGENS
CELL CYCLE
COLONY FORMATION
DISEASES
DRUGS
HETEROCYCLIC COMPOUNDS
KETONES
LUNGS
MALES
MAMMALS
MAN
MEN
NEOPLASMS
NICOTINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
PATHOGENESIS
PRIMATES
PYRIDINES
PYRROLES
PYRROLIDINES
RESPIRATORY SYSTEM
RESPIRATORY TRACT CELLS
SOMATIC CELLS
TOBACCO
TOXICITY
VERTEBRATES