Carcinogenic properties of pharmaceutical agents evaluated in the <i>IARC Monographs</i> programme

Marselos, Marios; Vainio, Harri

doi:10.1093/carcin/12.10.1751

Cited by 63 publications

(22 citation statements)

References 172 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although acriflavine has been discussed as a potentially carcinogenic and mutagenic substance due to its nuclear staining properties, no evidence for this has been found in epidemiological studies [12]. Therefore, acriflavine was described as a group 3 (''not classifiable as to its carcinogenicity to humans'') carcinogen by International Agency for Research on Cancer reports in 1987 and 1991 [13,14] and has been classified as ''probably not carcinogenic to humans'' [14]. Furthermore, data on the long-term use of orally administered acriflavine for HIV therapy did not show an increase in tumour rate in this population at high risk for neoplastic diseases [15][16][17].…”

Section: Staining Agentmentioning

confidence: 99%

Confocal laser endomicroscopy for diagnosing lung cancerin vivo

et al. 2012

View full text Add to dashboard Cite

Confocal laser endomicroscopy is a novel endoscopic technique that may allow imaging of living cells in lung tissue in vivo. We assessed the potential of this technique for the detection of histology during screening bronchoscopy for lung cancer.32 patients with suspected malignancies underwent bronchoscopy with endomicroscopy using acriflavine hydrochloride. Standardised areas and localised lesions were analysed by in vivo confocal imaging during bronchoscopy and biopsies were taken. Confocal images were graded and correlated prospectively with conventional histology from biopsies.Acriflavine hydrochloride yielded high-quality confocal images and strongly labelled airway epithelial cells. No side-effects were noted. 75 522 confocal images from 56 different locations were compared prospectively with histological data from biopsy specimens. Endomicroscopy allowed subsurface imaging with detailed analysis of cellular and subcellular structures. Neoplastic changes could be predicted with high accuracy (sensitivity 96.0%, specificity 87.1%, accuracy 91.0%).Confocal laser endomicroscopy with acriflavine is a novel diagnostic tool for the analysis of living cells during bronchoscopy and permits virtual histology of neoplastic changes in the airways with high accuracy. This technique may enable the rapid diagnosis of neoplasia during ongoing endoscopy in patients with suspected lung cancer.

show abstract

Section: Staining Agentmentioning

confidence: 99%

Confocal laser endomicroscopy for diagnosing lung cancerin vivo

et al. 2012

View full text Add to dashboard Cite

show abstract

“…If this were true the 3-MeA specific inducer Me-lex can be considered a new potential antineoplastic agent. Furthermore, it might be expected that such a compound would combine a high cytotoxicity and a low mutagenicity, avoiding (or diminishing) the undesired and well documented carcinogenic property of alkylating agents used in cancer therapy (14,15). Therefore, Me-lex may potentially have a higher therapeutic index with respect to other antineoplastic compounds.…”

mentioning

confidence: 99%

Relationship between DNA Methylation and Mutational Patterns Induced by a Sequence Selective Minor Groove Methylating Agent

Kelly¹,

Inga²,

Chen³

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

Me-lex, a methyl sulfonate ester appended to a neutral N-methylpyrrolecarboxamide-based dipeptide, was synthesized to preferentially generate N 3 -methyladenine (3-MeA) adducts which are expected to be cytotoxic rather than mutagenic DNA lesions. In the present study, the sequence specificity for DNA alkylation by Me-lex was determined in the p53 cDNA through the conversion of the adducted sites into single strand breaks and sequencing gel analysis. In order to establish the mutagenic and lethal properties of Me-lex lesions, a yeast expression vector harboring the human wild-type p53 cDNA was treated in vitro with Me-lex, and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. The results showed that: 1) more than 99% of the lesions induced by Me-lex are 3-MeA; 2) the co-addition of distamycin quantitatively inhibited methylation at all minor groove sites; 3) Me-lex selectively methylated A's that are in, or immediately adjacent to, the lex equilibrium binding sites; 4) all but 6 of the 33 independent mutations were base pair substitutions, the majority of which (17/33; 52%) were AT-targeted; 5) AT 3 TA transversions were the predominant mutations observed (13/33; 39%); 6) 13 out of 33 (39%) independent mutations involved a single lex-binding site encompassing positions A 600 -602 and 9 occurred at position 602 which is a real Me-lex mutation hotspot (n ‫؍‬ 9, p < 10 ؊6 , Poisson's normal distribution). A hypothetical model for the interpretation of mutational events at this site is proposed. The present work is the first report on mutational properties of Me-lex. Our results suggest that 3-MeA is not only a cytotoxic but also a premutagenic lesion which exerts this unexpected property in a strict sequence-dependent manner.

show abstract

“…Pharmaceutical ager&'&rcinogenig for humans provide data on exposures to relatively pure substances at well-defined dosages. Of the 20 pharmaceuticals considered conclusively to be human carcinogens, the similarity between humans and animals is remarkable with 85% concordance with respect to the organs affected by cancer (25). For the cases of positive rodent pharmaceutical studies with negative human data, the human studies often do not have sufficient sensitivity to detect a positive effect (1 7).…”

Section: Discussionmentioning

confidence: 99%

Rodent Carcinogenicity Bioassay: Past, Present, and Future

1994

View full text Add to dashboard Cite

Toxicitykarcinogenicity studies in rodents have played a pivotal role in identifying chemicals that are potentially hazardous to humans. In fact, nearly all of the known human carcinogens are also carcinogenic in 1 or more rodent species. During the past 20 yr the quality and consistency of rodent studies has improved considerably, and much has been learned about mechanisms whereby chemicals initiate or promote the carcinogenic process in rats and mice. The process of identifying chemicals that cause toxicity or carcinogenicity in rodents is quite well established, but the procedures for extrapolating this data for risk management decisions in the protection of human health have lagged far behind. While many would accept the assumptions that genotoxic chemicals that cause cancer in animals pose a cancer risk to humans and that genotoxic chemicals causing cancer at high doses pose a risk at lower doses, there is much less certainty with respect to nongenotoxic chemicals. The confusion about risk extrapolation for nongenotoxic chemicals has often lead to criticism of the hazard identification process for chemicals in general. There is increasing awareness of the complexity of the carcinogenic process that has made species extrapolation and dose extrapolation from rodent studies to humans more complex. Although newer molecular biological techniques and cell kinetic measurements offer exciting possibilities for better risk assessment, it is the combination of welldesigned rodent studies with appropriate mechanistic studies that offers the best hope for regulatory decisions based on sound scientific principles._.

show abstract

Carcinogenic properties of pharmaceutical agents evaluated in the IARC Monographs programme

Cited by 63 publications

References 172 publications

Confocal laser endomicroscopy for diagnosing lung cancerin vivo

Confocal laser endomicroscopy for diagnosing lung cancerin vivo

Relationship between DNA Methylation and Mutational Patterns Induced by a Sequence Selective Minor Groove Methylating Agent

Rodent Carcinogenicity Bioassay: Past, Present, and Future

Contact Info

Product

Resources

About