The genotoxic substances induce damage to the genetic material in the cells through interactions with the DNA sequence and structure. For example, the transition metal chromium interacts with DNA in its high-valent oxidation state so to incur DNA lesions leading to carcinogenesis. The metastable oxidation state Cr(V) is achieved through reductive activation. The researchers performed an experiment to study the interaction between DNA with the carcinogenic chromium by using a Cr(V)-Salen complex at the specific oxidation state.[3] The interaction was specific to the guanine nucleotide in the genetic sequence. In order to narrow the interaction between the Cr(V)-Salen complex with the guanine base, the researchers modified the bases to 8-oxo-G so to have site specific oxidation. The reaction between the two molecules caused DNA lesions; the two lesions observed at the modified base site were guanidinohydantoin and spiroiminodihydantoin. To further analyze the site of lesion, it was observed that polymerase stopped at the site and adenine was inappropriately incorporated into the DNA sequence opposite of the 8-oxo-G base.
https://en.wikipedia.org/wiki/Genotoxicity
| Mechanism | Examples | |
|---|---|---|
| Alkylating agents | interfere with DNA replication and transcription by modifying DNA bases. | Busulfan, Carmustine, Mechlorethamine |
| Intercalating agents | interfere with DNA replication and transcription by wedging themselves into the spaces in between DNA's nucleotides | Daunorubicin, Doxorubicin, Epirubicin |
| Enzyme inhibitors | inhibit enzymes that are crucial to DNA replication | Decitabine, Etoposide, Irinotecan |
No comments:
Post a Comment