Toxicology

Genotoxicity

TRGenotoksisite
Also known as:Genetic toxicity

The property of a chemical or physical agent to damage genetic material, causing gene mutations, structural chromosome aberrations or changes in chromosome number that may lead to cancer or heritable defects.

In depth

The term covers mutagenicity (gene mutations), clastogenicity (chromosome breakage) and aneugenicity (numerical changes, e.g. via spindle disruption). Alkylating agents and other DNA-reactive compounds form DNA adducts, directly or after metabolic activation; others act through intercalation, topoisomerase inhibition or oxidative damage. Under ICH S2(R1), a bacterial reverse mutation (Ames) test with and without metabolic activation (S9) is combined with mammalian chromosomal-damage assays in vitro and/or in vivo, such as the micronucleus test.

DNA-reactive mutagens are conventionally assumed to act without a safe threshold. Genotoxic cytotoxics can cause therapy-related myeloid neoplasms and germ-cell damage, and ICH M7 governs the control of mutagenic impurities such as N-nitrosamines.

Clinical pearl

Genotoxic cytotoxics are hazardous drugs: prepare them in a biological safety cabinet with appropriate protective equipment, and counsel both men and women on contraception during and after treatment as specified in the SmPC/KÜB.

Example drugs

Cyclophosphamide Chlorambucil Doxorubicin Etoposide Azathioprine
TRIn Turkish

Genotoksisite

Kimyasal ya da fiziksel bir etkenin genetik materyale zarar vererek gen mutasyonlarına, yapısal kromozom anomalilerine veya kromozom sayısında değişikliklere yol açabilme özelliğidir; bu hasar kansere ya da kalıtsal bozukluklara neden olabilir.

Kavram mutajeniteyi (gen mutasyonları), klastojeniteyi (kromozom kırıkları) ve anöjeniteyi (ör. iğ ipliğinin bozulmasıyla kromozom sayısı değişiklikleri) kapsar. Alkilleyici ajanlar ve DNA ile tepkimeye giren diğer bileşikler, doğrudan ya da metabolik aktivasyon sonrasında DNA addüktleri oluşturur; diğerleri interkalasyon, topoizomeraz inhibisyonu veya oksidatif hasar yoluyla etki eder. ICH S2(R1) kılavuzunda, metabolik aktivasyonlu ve aktivasyonsuz (S9) bakteriyel geri mutasyon (Ames) testi, mikronükleus testi gibi in vitro ve/veya in vivo memeli kromozom hasarı testleriyle birlikte uygulanır.

DNA ile tepkimeye giren mutajenlerin geleneksel olarak güvenli bir eşik olmaksızın etki ettiği varsayılır. Genotoksik sitotoksik ilaçlar tedaviye bağlı miyeloid neoplazilere ve germ hücre hasarına yol açabilir; N-nitrozaminler gibi mutajenik safsızlıkların kontrolü ICH M7 kılavuzuna tabidir.

Genotoksik sitotoksik ilaçlar tehlikeli ilaç sınıfındadır: biyolojik güvenlik kabininde ve uygun koruyucu ekipmanla hazırlanmalı; hem erkek hem kadın hastalara, tedavi süresince ve sonrasında KÜB’de belirtildiği şekilde kontrasepsiyon danışmanlığı verilmelidir.

Diğer adları:Genetik toksisite · Genotoksik etki
Updated 24.09.2026 0 views Educational reference — verify against current sources before clinical use.

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