Genotoxicity induced in CD-1 mice by inhaled lead: differential organ response.
Lead is perhaps the longest used and best recognized toxic environmental chemical and it is still being used recklessly. Lead (Pb) has been found to be capable of eliciting a positive response in an extraordinarily wide range of biological and biochemical tests; among them tests for enzyme inhibition, fidelity of DNA synthesis, mutation, chromosomal aberrations, cancer and birth defects. Since inhalation is one of the most important routes of environmental Pb exposure, in the present study a lead inhalation model in mice was implemented in order to detect the induction of genotoxic damage as single-strand breaks and alkali-labile sites in several mouse organs (nasal epithelial cells, lung, whole blood, liver, kidney, bone marrow, brain and testes), assessed by single cell gel electrophoresis (SCGE) or Comet assay. We found differences among the organs studied after a single and subsequent inhalations: in the organs analyzed we observed a positive induction of DNA damage after a single inhalation only in the liver and the lung. In subsequent inhalations the response was positive in all organs except the testicle, however, DNA damage induction over time was different for each organ. A correlation between length of exposure, DNA damage and metal tissue concentration was observed for lung, liver and kidney. Differences in DNA damage occurred in organs when lead acetate was administered acutely or sub-chronically. These results show that lead acetate inhalation induces systemic DNA damage but that some organs are special targets of this metal, such as lung and liver, depending in part on length of exposure, suggesting alternative organ processes to handle lead intoxication.
Valverde
Mahara
M
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, Ciudad Universitaria, 04510 México DF, Mexico.
Fortoul
Teresa I
TI
Díaz-Barriga
Fernando
F
Mejía
Jesús
J
del Castillo
Emilio Rojas
ER
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D001773:Blood Cells / Q000737:chemistry / Q000187:drug effects; D001854:Bone Marrow Cells / Q000737:chemistry / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D005269:Femur / Q000737:chemistry / Q000187:drug effects; D007668:Kidney / Q000737:chemistry / Q000187:drug effects; D007855:Lead Poisoning / Q000235:genetics / Q000473:pathology; D007962:Leukocytes / Q000737:chemistry / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009300:Nasal Septum / Q000737:chemistry / Q000187:drug effects; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D013054:Spectrophotometry, Atomic; D013737:Testis / Q000737:chemistry / Q000187:drug effects; D013997:Time Factors
D000393:Air Pollutants; D009942:Organometallic Compounds; C008261:lead acetate