Abstract
Lufenuron, a benzoylurea insecticide that inhibits chitin synthesis, was evaluated for its cytogenotoxic and DNA-damaging effects on Allium cepa root meristem cells using root growth inhibition, Allium anaphase-telophase, comet, RAPD-PCR, and flow cytometry assays. Molecular docking was also performed to investigate the interactions of lufenuron with cytochrome P450 enzymes (CYP81A12 and CYP81A21) and a standard B-form double-stranded DNA dodecamer model (12 base pairs). Root growth significantly decreased from 3.87 ± 0.44 cm at low doses to 0.26 ± 0.12 cm at high concentrations according to the root growth inhibition test. Lufenuron exposure caused dose- and time-dependent reductions in mitotic index (MI) and increases in chromosomal aberrations (CAs) in anaphase-telophase cells such as disturbed anaphase-telophase, chromosomal laggards, stickiness, anaphase bridges) and other cells (micronuclues and c-metaphase) along with DNA damage. The results of flow cytometry demonstrated the existence of subG1 arrest-induced early apoptosis. Compared with the negative control, lufenuron-treated roots exhibited distinct RAPD polymorphisms characterized by the loss and/or emergence of specific DNA bands. Numerical and phenetic analyses of RAPD profiles clearly demonstrated a dose- and time-dependent genotoxic response to lufenuron exposure. Molecular docking studies showed that lufenuron binds strongly to CYP81A12, CYP81A21, and DNA with greater affinity than the positive control (MMS), fitting into enzyme active sites and the DNA minor groove with an intercalation gap. Overall, the study demonstrates that lufenuron exerts notable cytogenotoxic and DNA-damaging effects on A. cepa roots. Therefore, its agricultural use should be carefully regulated to minimize potential risks to non-target organisms and environmental health.