Assessment of genotoxic effects by lindane.
The well known and previously widespread insecticide lindane has been re-assessed for DNA-damaging activity. A first group of investigations using standard in vitro and in vivo mutagenicity assays did not indicate any genotoxic effects of lindane at all. The assay systems used were for the induction of HPRT mutations and sister chromatid exchanges in CHO cells cultured in vitro, and for micronuclei induction in vivo in bone marrow cells of rats, hamsters and mice. Also, lindane was assessed for its potential to induce sister chromatid exchanges in vivo in the bone marrow of Chinese hamsters. These specific assay systems had not been used previously for elucidating the genotoxic effects of this compound, but they are basically similar to other standard mutagenicity assays in which lindane has been shown to be devoid of genotoxic activity. The second part of the investigations was directed at re-evaluating a previously reported positive effect of the compound in primary rat hepatocytes in vitro. We performed in vitro and in vivo studies with hepatocytes from the rat liver and used alkaline elution to detect DNA damage. However, we could not demonstrate that lindane induced genotoxicity, unless considerable concomitant cytotoxicity was apparent as well. Finally, since lindane can be ingested and inhaled by humans, we also measured the induction of DNA damage in local target organs of absorption using single cell micro-gel-electrophoresis (the comet assay). In these cases lindane was genotoxic in cells of the gastric and nasal mucosa in vitro and also in vivo following appropriate routes of application (oral and inhalational exposure).
Pool-Zobel
B L
BL
Institut für Hygiene und Toxikologie, Bundesforschungsanstalt für Ernährung, Karlsruhe, Germany.
Guigas
C
C
Klein
R
R
Neudecker
C
C
Renner
H W
HW
Schmezer
P
P
D000280:Administration, Inhalation; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016466:CHO Cells / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D003106:Colon / Q000166:cytology / Q000187:drug effects; D006224:Cricetinae; D004249:DNA Damage; D004586:Electrophoresis; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects; D001556:Hexachlorocyclohexane / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001556:Hexachlorocyclohexane