Genotoxicity of di‐butyl‐phthalate and di‐iso‐butyl‐phthalate in human lymphocytes and mucosal cells

Abstract

The genotoxicity of phthalates, widely used plasticizers, has been shown previously for di-butyl-phthalate (DBP) and di-iso-butyl-phthalate (DBP) in human mucosal cells of the upper aerodigestive tract in a previous study using the Comet assay. Furthermore, higher genotoxic sensitivities of patients with squamous cell carcinomas of either the larynx or the oropharynx compared to non-tumor patients were described. Other authors have demonstrated DNA damage by a different phthalate in human lymphocytes. It was the aim of the present study to determine whether there is a correlation between the genotoxic sensitivities to DBP and its isomer DiBP in either mucosal cells or lymphocytes. The single-cell microgel electrophoresis assay (Comet assay) was applied to detect DNA strand breaks in human epithelial cells of the upper aerodigestive tract (n=132 specimens). Human mucosa was harvested from the oropharynx in non-tumor patients and patients with squamous cell carcinomas of the oropharynx. Laryngeal mucosa of patients with laryngeal squamous cell carcinomas was harvested as well. Peripheral lymphocytes (n=49 specimens) were separated from peripheral blood. Xenobiotics investigated were DBP, DiBP, and N'methyl-N'-nitro-N-nitrosoguanidine (MNNG) as positive control, respectively. For statistical analysis, the SPSS correlation analysis according to Pearson and the Wilcoxon test were performed. Genotoxicity was found for DBP and DiBP in epithelial cells and lymphocytes (P<0.001). MNNG caused severe DNA damage. In analyzing DBP and DiBP results, genotoxic impacts in mucosal cells showed an intermediate correlation (r=0.570). Correlation in lymphocytes was the same (r=0.570). Phthalates have been investigated as a potential health hazard for a variety of reasons, including possible xenoestrogenic impact, peroxisome proliferation, and membrane destabilization. The present investigation suggests a correlated DNA-damaging impact of DBP and DiBP in human mucosal cells and in lymphocytes, respectively.

The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay.

“…Using the alkaline comet assay, researchers have found evidence of genotoxicity with in vitro studies examining lymphocytes and mucosal cells of the upper aerodigestive tract after exposure to DBP and DiBP (Kleinsasser et al 2000a(Kleinsasser et al , 2000b(Kleinsasser et al , 2001. In another study using the alkaline comet assay on human leukocytes, an association between MEHP and DEHP and increased tail moments was found (Anderson et al 1999).…”

Gestational and lactational exposition to Di-N-butyl-phthalate (DBP) increases inflammation and preneoplastic lesions in prostate of wistar rats after carcinogenicN-methyl-N-nitrosourea (MNU) plus testosterone protocol

“…However, a significant increase in the PIN and inflammatory focus incidence in TDBP500 animals was observed compared to CN and CMNU. This increase in the incidence of lesions with higher malignant potential in TDBP500 animals may be related to an increase in genetic instability caused by the high DBP dose (Kleinsasser et al, ), activation of cell pathways linked to GPR30 by DBP (Maggiolini and Picard, ; Hu et al, ) or, genetic or epigenetic marks that modulate these pathways.…”

Assessment of hormonal activities and genotoxicity of industrial effluents using in vitro bioassays combined with chemical analysis

“…Some environmental estrogenic compounds including BPA, 4-NP, 4-t-OP, and their ethoxylates, have shown mutagenic effects in in vitro or in vivo assays [51][52][53][54][55][56]. Phthalate compounds, including dibutyl phthalate, diisobutyl phthalate, bis (2-ethylhexyl) phthalate, and mono-2-ethylhexyl phthalate, have potential mutagenic and carcinogenic effects on organisms and trick a possible pathway of tumor initiation in animals [57][58][59][60][61]. Aniline is nonmutagenic [62][63][64], but its derivates such as 2,4-dimethylaniline and 2,4,6-trimethylaniline were identified as mutagens and carcinogens [65].…”