Diagnostic Microdosing Approach to Study Gemcitabine Resistance.
Tiffany M. Scharadin, Hongyong Zhang, Maike Zimmermann, Sisi Wang, Michael Malfatti, George Cimino, Kenneth W. Turteltaub, Ralph W. de Vere White, Chong-Xian Pan, Paul T. Henderson
Chemical Research in Toxicology November 21, 2016 DOI: 10.1021/acs.chemrestox.6b00247 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro cell line study Peer reviewed |
|---|---|
| Population | Two nearly isogenic bladder cancer cell lines differing in resistance to several chemotherapy drugs |
| Intervention | Gemcitabine |
| Duration | 4-24 h treatment |
| Topics | Microdosing |
| Key points | Gemcitabine is incorporated into DNA of bladder cancer cells at subtherapeutic "microdose" concentrations, and incorporation levels correlate with drug cytotoxicity. The authors report that RRM2 substantially mediates gemcitabine toxicity and propose DNA gemcitabine levels as a potential biomarker of cytotoxicity. |
Abstract
Gemcitabine metabolites cause the termination of DNA replication and induction of apoptosis. We determined whether subtherapeutic "microdoses" of gemcitabine are incorporated into DNA at levels that correlate to drug cytotoxicity. A pair of nearly isogenic bladder cancer cell lines differing in resistance to several chemotherapy drugs were treated with various concentrations of 14C-labeled gemcitabine for 4-24 h. Drug incorporation into DNA was determined by accelerator mass spectrometry. A mechanistic analysis determined that RRM2, a DNA synthesis protein and a known resistance factor, substantially mediated gemcitabine toxicity. These results support gemcitabine levels in DNA as a potential biomarker of drug cytotoxicity.
Comparable studies
Other preclinical and animal studies on microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats Wistar rats | 2018 | Experimental study | n = 40 |
| Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats. Rats | 2023 | Experimental study | |
| Repeated microdoses of LSD do not alter anxiety or boldness in zebrafish. Zebrafish (Danio rerio) | 2024 | Experimental study | |
| Application of microarray patches for the transdermal administration of psychedelic drugs in micro-doses. Excised neonatal porcine skin and rats | 2025 | Experimental study | |
| Toward Predicting Acute Myeloid Leukemia Patient Response to 7 + 3 Induction Chemotherapy via Diagnostic Microdosing Paired sensitive and resistant cancer cell lines, AML cell lines, and 10 viably... | 2018 | Preclinical cell line study with a pilot retrospective analysis of primary patient samples | n = 10 |