Chromosomal instability in amniocytes from fetuses of mothers who smoke: Editorial comment

Tobacco contains many mutagenic compounds, and tobacco-specific metabolites have recently been found in fetal blood and cell-free amniotic fluid. This study examined possible genotoxic effects of maternal smoking on amniotic fluid cells. Chromosomal instability in the form of chromosomal gaps and breaks was sought along with structural chromosomal abnormalities. Amniocytes were obtained by amniocentesis in a prospective series of 25 women who had smoked 10 or more cigarettes a day for at least 10 years and in 25 nonsmokers. Two independent observers assessed chromosomal stability in routine chromosome spreads in a blinded manner, and relevant break points were identified by G-banding.

Chromosomal instability was found in 10.5% of smokers and 8.0% of control subjects, and chromosomal lesions in 15.7% of smokers and 10.1% of control subjects. Rates of structural chromosomal abnormalities were 12.1% and 3.5%, respectively. Deletions and translocations were the most common structural abnormalities in both groups. No significant age effect was noted. Analysis of all 689 break points showed that band 11q23, a band commonly implicated in hematopoietic malignancies, was the most affected chromosomal region.

Increased chromosomal instability has been identified in amniocytes from women who smoke at least half a pack of cigarettes a day for 10 years or longer. Band 11q23, which is implicated in leukemogenesis, is apparently very sensitive to tobacco compounds. This band contains the genes ATM (cell prolymphocytic leukemia); PLZF (leukemia acute, promyelocytic; PLZF/RARA type); and MLL (leukemia, myeloid/lymphoid, or mixed lineage). Possibly, transplacental exposure to tobacco smoke is associated with an increased risk of hematopoietic malignancies in children.