Effect of ethylnitrosourea on HPRT gene in human promyelocytic leukemia cells.
OBJECTIVE
To explore the molecular spectra and mechanism of human hypoxanthine guanine phosphoribosyl transferase (HPRT) gene mutation induced by ethyluitrosourea (ENU).


METHODS
Single cell cloning culture, two-way screening, multiple PCR amplification and electrophoresis technique were used.


RESULTS
With dose of ENU increasing, cell plating efficiency reduced (in the group with 100-200 micro g/ml doses, P < 0.01) and mutation frequency increased (in the group with 12.5-200.0 micro g/ml doses, P < 0.05) significantly. There was no all exons deletion in spontaneous mutations, and only 7.7% of them were detected as single exon deletion. But, deletion was found in 79.7% of ENU-induced mutations (62.5%-89.4%, P < 0.01), and deletion mutations in all nine exons of HPRT gene. Most of ENU-induced mutations were chain deletion with multiple exons (88.1%).


CONCLUSIONS
The spectra in spontaneous mutations differed completely from ENU-induced ones. ENU was liable to cause bigger changes in genetic structure, which suggested a stronger ENU's mutagenesis.
Liu
Shengxue
S
Department of Health Toxicology, Third Military Medical University, Chongqing 400038, China.
Cao
Jia
J
An
Hui
H
D000477:Alkylating Agents / Q000494:pharmacology*; D005038:Ethylnitrosourea / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000473:pathology; D009154:Mutation / Q000187:drug effects*; D014410:Tumor Stem Cell Assay
D000477:Alkylating Agents; D007041:Hypoxanthine Phosphoribosyltransferase; D005038:Ethylnitrosourea