Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 368

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules

Open access
Tolcher, A W, Gerson, S L, Denis, L, Geyer, C, Hammond, L A, Patnaik, A, Goetz, A D, Schwartz, G, Edwards, T, Reyderman, L, Statkevich, P, Cutler, D L, Rowinsky, E K·2003·British Journal of Cancer
DOI 10.1038/sj.bjc.6600827
Open this paper in CoChat — free account

Abstract

Temozolomide, an oral DNA methylator that inactivates the DNA repair enzyme O(6)-alkylguanine-DNA alkyltransferase (AGAT), has demonstrated anticancer activity on protracted schedules. Protracted schedules may lead to an 'autoenhancement' of temozolomide's inherent cytotoxic potential by cumulative reduction of the cell's capacity for AGAT-mediated DNA repair and resistance. This study was undertaken to characterise AGAT inactivation and regeneration in the peripheral blood mononuclear cells (PBMCs) of patients treated on two protracted temozolomide schedules. O(6)-alkyl guanine-DNA alkyltransferase activity was measured in the PBMCs of patients treated on two phase I protracted temozolomide studies. Patients were treated daily for either 7 days every 2 weeks (Schedule A) or 21 days every 4 weeks (Schedule B). The effects of various temozolomide doses (75-175 mg m(-2)), treatment duration (7-21 days), and temozolomide plasma levels on AGAT inactivation and regeneration, as well as the relation between AGAT inactivation and toxicity, were studied. O(6)-alkyl guanine-DNA alkyltransferase activity in PBMCs was measured serially in 52 patients. Marked inactivation of AGAT occurred following 7 days of temozolomide treatment, with mean AGAT activity decreasing by 72% (P<0.0001). Similarly, mean AGAT activity decreased by 63 and 73% after 14 and 21 days of treatment, respectively (P<0.001 for both comparisons). O(6)-alkyl guanine-DNA alkyltransferase inactivation was greater after 7 days of treatment with higher doses of temozolomide than lower doses and remained markedly reduced 7 days post-treatment. However, AGAT inactivation following temozolomide treatment for 14 and 21 days was similar at all doses. On the continuous 21-day schedule, AGAT inactivation was significantly greater in patients who experienced severe thrombocytopenia than those who did not (90.3+/-5.5 vs 72.5+/-16.1%, P<0.045). In conclusion, protracted administration of temozolomide, even at relatively low daily doses, leads to significant and prolonged depletion of AGAT activity, which may enhance the antitumour activity of the agent.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/sj.bjc.6600827

Cites

20 of 20 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 20 references

Cited by

See all 368

Metadata

Authors
Tolcher, A. W., Gerson, S. L., Denis, L., Geyer, C., Hammond, L. A., Patnaik, A., Goetz, A. D., Schwartz, G., Edwards, T., Reyderman, L., Statkevich, P., Cutler, D. L., & Rowinsky, E. K.
Venue
British Journal of Cancer
Publisher
Springer Science and Business Media LLC
Published
2003-04
Volume
88
Issue
7
Pages
1004-1011
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
DOI
10.1038/sj.bjc.6600827
OpenAlex
W1984955359
Cited by
368
References
20
FWCI
6.43
Type
journal article
Language
en
Open access
hybrid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. https://app.cochat.ai/papers/10.1038/sj.bjc.6600827
The paper
Tolcher, A. W., Gerson, S. L., Denis, L., Geyer, C., Hammond, L. A., Patnaik, A., Goetz, A. D., Schwartz, G., Edwards, T., Reyderman, L., Statkevich, P., Cutler, D. L., & Rowinsky, E. K. (2003). Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. British Journal of Cancer. https://doi.org/10.1038/sj.bjc.6600827

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.