Mutagenesis and comutagenesis by lead compounds

https://doi.org/10.1016/0165-1218(92)90034-WGet rights and content

Abstract

We have previously reported that lead(II) is weakly mutagenic to Chinese hamster V79 cells. A transgenic cell line G12 containing a single copy of the E. coli gpt gene was developed in this laboratory from Chinese hamster V79 cells. The gpt locus in the G12 cells is more mutable by radiation and oxidative agents compared with the endogenous hprt locus of wild-type V79 cells. We have investigated the mutagenicity of two lead compounds at the gpt locus in G12 cells. Only at a toxic dose is lead acetate significantly mutagenic to G12 cells. Lead nitrate is not significantly mutagenic at any dose. Although both compounds are water-soluble, lead acetate, but not lead nitrate, forms a fine white insoluble precipitate upon addition to growth medium. A nick translation assay on cells treated with lead compounds and then permeabilized indicated that lead nitrate and, to a greater extent, lead acetate causes the appearance of nicks in chromosomal DNA. Lead ions in the presence of hydrogen peroxide, but not alone, introduced nicks into supercoiled plasmid DNA in vitro, suggesting that lead ions can partake in a Fenton reaction and thereby damage DNA. At lower nonmutagenic concentrations, lead acetate enhances the mutagenicity of MNNG and ultraviolet light. DNA damage by ultraviolet light is not enhanced by lead ions in vitro. Our data support the concept that non-toxic concentrations of lead(II) can inhibit DNA repair. Thus, at biologically relevant doses, lead(II) could act as a comutagen and possibly a cocarcinogen, but is not likely to act as an initiating genotoxic carcinogen.

References (25)

  • C.B. Klein et al.

    Transgenic Chinese hamster V79 cell lines which exhibit variable levels of gpt mutagenesis

    Environ. Mol. Mutagen

    (1990)
  • C.B. Klein et al.

    Two transgenic gpt+ V79 cell lines differ in their mutagenic responsiveness to clastogens

    Environ. Mol. Mutagen.

    (1991)
  • Cited by (85)

    • Data Needs, Availability, Sources, and Reliability

      2017, Risk Management of Complex Inorganic Materials: A Practical Guide
    • Vitamin E modifies the ultrastructure of testis and epididymis in mice exposed to lead intoxication

      2013, Annals of Anatomy
      Citation Excerpt :

      In addition, children living in houses built before 1978 in the USA with lead-base water pipes or paint may have higher than normal blood lead levels (Brown and Margolis, 2012). Lead toxicity, whether occupational or otherwise, therefore, is a great concern because it has been implicated in a variety of health conditions including neurological (Perlstein and Attala, 1966; Han et al., 2007) and cancer (Roy and Rossman, 1992; Patra et al., 2001) disorders in humans. Lead toxicity has been shown to impair sperm shape and reduce the number of cells in semen (Acharya et al., 1997; Eyden et al., 1978).

    • Lead acetate does not inhibit dimethylnitrosamine activation and interacts with phenobarbital which is genotoxic in the ST cross of the Drosophila wing spot test

      2011, Food and Chemical Toxicology
      Citation Excerpt :

      Lead has been proven to be a major pollutant with diverse effects on living organisms (Beck, 1992; Calabrese and Baldwin, 1992; Johnson, 1998; Roy and Rossman, 1992).

    • Carcinogenic and genotoxic effects of lead in human populations

      2011, Trace Metals and other Contaminants in the Environment
      Citation Excerpt :

      DNA damage was not observed by Roy and Rossman (1992) but was seen by Robbiano et al. (1999).

    View all citing articles on Scopus
    View full text