Transgenerational reproductive toxicity of 2,4,6-trinitrotoluene (TNT) and its metabolite 4-ADNT in Caenorhabditis elegans

Abstract

2,4,6-trinitrotoluene (TNT) as an energetic compound widely used in military applications has aroused great concerns in recent years due to its large-scale contamination in soil and water; however, its toxicity is still largely unknown. In this study, we investigated the reproductive toxicity and the transgenerational effects of TNT on Caenorhabditis elegans (C. elegans). Our data showed that exposure to TNT at concentrations ranging from 10 to 100 ng/mL resulted in decreasing the lifespan, brood size, number of oocytes and eggs in uterus, while increasing the number of germ cell apoptosis in C. elegans. The apoptotic effects of TNT were blocked in mutants of cep-1 (w40), egl-1 (n487), and hus-1 (op241), indicating conserved genotoxic response genes was involved in mediating TNT-induced germ cell apoptosis. Parental exposure to TNT significantly increased the germ cell apoptosis from P0 to F2 generation, but the toxicity faded away in F3 and F4 generations. Furthermore, TNT was rapidly metabolized in P0, and the accumulation of 4-aminodinitrotoluene (4-ADNT), the main metabolite of TNT in C. elegans, showed a significant decrease from P0 to F1 and a slow decrease in the subsequent generations. Our results demonstrated that ingested TNT can cause severe transgenerational reproductive toxicity and be rapidly converted to 4-ADNT in the nematodes. These data provided basis for future studies on the effects of energetic compounds across generations.

Keywords: 4-ADNT; C. elegans; Reproductive toxicity; TNT; Transgenerational effects.