Light-induced toxic effects of tamoxifen: A chemotherapeutic and chemopreventive agent

Wang, Shuguang; Wang, Lei; Yin, Jun‐Jie; Wang, Zheng; Fu, Peter P.; Yu, Hongtao

doi:10.1016/j.jphotochem.2008.09.013

Cited by 12 publications

(11 citation statements)

References 51 publications

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“… 174 , 190 The wide discrepancy arguably results from a combination of two factors: (1) differences in the sensitivity of the means by which the cornea is assessed, and (2) the subtlety of the deposits. 190 However, other hypothetically pertinent factors (e.g., amount of sunlight exposure) 191 might also affect the observed frequencies. Regardless, even readily observable corneal deposits are reversible 174 and not sight-threatening.…”

Section: Adjuvant Endocrine Therapymentioning

confidence: 99%

Breast Cancer Medications and Vision: Effects of Treatments for Early-stage Disease

Eisner¹,

Luoh²

2011

Current Eye Research

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This review concerns the effects on vision and the eye of medications prescribed at three phases of treatment for women with early-stage breast cancer (BC): (1) adjuvant cytotoxic chemotherapy, (2) adjuvant endocrine therapy, and (3) symptomatic relief. The most common side effects of cytotoxic chemotherapy are epiphora and ocular surface irritation, which can be caused by any of several different regimens. Most notably, the taxane docetaxel can lead to epiphora by inducing canalicular stenosis. The selective-estrogen-receptor-modulator (SERM) tamoxifen, long the gold-standard adjuvant-endocrine-therapy for women with hormone-receptor-positive BC, increases the risk of posterior subcapsular cataract. Tamoxifen also affects the optic nerve head more often than previously thought, apparently by causing subclinical swelling within the first 2 years of use for women older than ∼50 years. Tamoxifen retinopathy is rare, but it can cause foveal cystoid spaces that are revealed with spectral-domain optical coherence tomography (OCT) and that may increase the risk for macular holes. Tamoxifen often alters the perceived color of flashed lights detected via short-wavelength-sensitive (SWS) cone response isolated psychophysically; these altered perceptions may reflect a neural-response sluggishness that becomes evident at ∼2 years of use. The aromatase inhibitor (AI) anastrozole affects perception similarly, but in an age-dependent manner suggesting that the change of estrogen activity towards lower levels is more important than the low estrogen activity itself. Based on analysis of OCT retinal thickness data, it is likely that anastrozole increases the tractional force between the vitreous and retina. Consequently, AI users, myopic AI users particularly, might be at increased risk for traction-related vision loss. Because bisphosphonates are sometimes prescribed to redress AI-induced bone loss, clinicians should be aware of their potential to cause scleritis and uveitis occasionally. We conclude by suggesting some avenues for future research into the visual and ocular effects of AIs, particularly as relates to assessment of cognitive function.

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Section: Adjuvant Endocrine Therapymentioning

confidence: 99%

Breast Cancer Medications and Vision: Effects of Treatments for Early-stage Disease

Eisner¹,

Luoh²

2011

Current Eye Research

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“…While advances in target identification, chemical synthesis, and in vitro analysis have led to improvements in drug development, less progress has been made in improving toxicity and efficacy assays. The most common assay for mutagenicity is the bacteria-based Ames test (Mortelmans and Zeiger 2000), which has been used to assess the mutagenicity, photomutagenicity, and phototoxicity of chemotherapeutics (Wang et al 2009). The efficacy of the Ames test is limited because bacteria lack many of the genes responsible for the xenobiotic metabolism of drugs and have different DNA damage repair pathways to eukaryotes, and the test only assays the reversion frequency of a single mutation.…”

Section: Discussionmentioning

confidence: 99%

A Multimodal Genotoxic Anticancer Drug Characterized by Pharmacogenetic Analysis in Caenorhabditis elegans

Hamza

Singh

et al. 2020

Genetics

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New anticancer therapeutics require extensive in vivo characterization to identify endogenous and exogenous factors affecting efficacy, to measure toxicity and mutagenicity, and to determine genotypes that result in therapeutic sensitivity or resistance. We used Caenorhabditis elegans as a platform with which to characterize properties of the anticancer therapeutic CX-5461. To understand the processes that respond to CX-5461-induced damage, we generated pharmacogenetic profiles for a panel of C. elegans DNA replication and repair mutants with common DNA-damaging agents for comparison with the profile of CX-5461. We found that multiple repair pathways, including homology-directed repair, microhomology-mediated end joining, nucleotide excision repair, and translesion synthesis, were needed for CX-5461 tolerance. To determine the frequency and spectrum of CX-5461-induced mutations, we used a genetic balancer to capture CX-5461-induced mutations. We found that CX-5461 is mutagenic, resulting in both large copy number variations and a high frequency of single-nucleotide variations (SNVs), which are consistent with the pharmacogenetic profile for CX-5461. Whole-genome sequencing of CX-5461-exposed animals found that CX-5461-induced SNVs exhibited a distinct mutational signature. We also phenocopied the CX-5461 photoreactivity observed in clinical trials and demonstrated that CX-5461 generates reactive oxygen species when exposed to UVA radiation. Together, the data from C. elegans demonstrate that CX-5461 is a multimodal DNA-damaging anticancer agent.

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“…The simultaneous activity of Type I and Type II photoprocesses, i.e., radical processes leading to DNA cleavage and energy transfer between ketoprofen and pyrimidines, was suggested (31). The chemotherapeutic and chemopreventive agent tamoxifen was found to be photomutagenic in S. typhimurium TA102 and DNAtamoxifen covalent adducts were identiˆed (32).…”

Section: Photogenotoxicity and Photomutagenicity Of Drugsmentioning

confidence: 99%

Photogenotoxicity and Photomutagenicity of Medicines, Carcinogens and Endogenous Compounds

Arimoto‐Kobayashi

2014

Genes and Environment

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Epidemiological studies suggest UVA play a signiˆcant role in the induction of skin cancers. Nucleic acids and proteins have extremely weak extinctions in UVA and visible light regions. The absorption of UVA energy is dependent on endogenous or exogenous sensitizers, and the photogenotoxicity of UVA is derived from the excited sensitizers. Photosensitive medicines, carcinogens and endogenous compounds can participate in UVA-induced photogenotoxicity and photomutagenicity. Irradiated medicines reported to be involved in photosensitization and phototoxicity such as antipsychotics, antihistamine agents, non-steroidal anti-in‰ammatory drugs, antihypertensive drugs, anti-diabetic agents, antibiotics, antifungal drugs and antibacterial agents. As an alternate pathway for activation, several carcinogens can be converted with UVA to reactive intermediates that bind DNA in the absence of the activation enzymes. Several endogenous compounds have also been reported to act photosensitizers. Photogenotoxicity and photomutagenicity are unwanted side-eŠects related to the UV-mediated activation of chemicals. In considering risks and beneˆts, the interrelationship between light, chemicals and human health remain an important topic of research.

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Light-induced toxic effects of tamoxifen: A chemotherapeutic and chemopreventive agent

Cited by 12 publications

References 51 publications

Breast Cancer Medications and Vision: Effects of Treatments for Early-stage Disease

Breast Cancer Medications and Vision: Effects of Treatments for Early-stage Disease

A Multimodal Genotoxic Anticancer Drug Characterized by Pharmacogenetic Analysis in Caenorhabditis elegans

Photogenotoxicity and Photomutagenicity of Medicines, Carcinogens and Endogenous Compounds

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