High Levels of Organochlorines Are Associated with Induction of ABL1 Promoter Methylation in Children with Acute Lymphoblastic Leukemia.

Abstract

Exposure to organochlorines is associated with epigenetic changes, including methylation change in the promoter of tumor suppressor genes, thereby leading to cancer induction. The aim of this study was to investigate the relationship between organochlorine pesticides (OCPs) and ABL1 promoter methylation in child patients with acute lymphoblastic leukemia (ALL) and the control group. The methylation rate of the ABL1 promoter was evaluated using the methylation-specific polymerase chain reaction method, and the level of OCPs in patients with ALL and healthy children was measured using gas chromatography. ABL1 promoter hypermethylation was observed in 64% of ALL patients and 28.5% of children in the control group. The level of OCPs in children with methylated ABL1 promoters was significantly higher than that in children with nonmethylated ABL1 promoters (p < 0.05). Our findings suggest that OCPs, especially alpha-hexachlorocyclohexane, beta-hexachlorocyclohexane, gamma-hexachlorocyclohexane, 2,4 dichlorodiphenyldichloroethylene, and 4,4 dichlorodiphenyltrichloroethane may induce methylation at the ABL1 promoter level, thereby preventing the normal expression of the ABL1 gene. As a result, the reduced expression of ABL1 (a tumor suppressor) gene due to the hypermethylation of its promoter leads to the disruption of normal biological processes, thus making cells vulnerable to oncogenic factors.