Reaction kinetic studies for comparison of mutagenic potency between butadiene monoxide and glycidamide

Motwani, HV; Eriksson, L; Göpfert, L; Larsen K
2018 | Chem. Biol. Interact. | 288 (57-64)

Parallelogram based approach for in vivo dose estimation of genotoxic metabolites in humans with relevance to reduction of animal experiments

2017 | Sci Rep | 7 (17560) (1-10)

Quantification of the mutagenic potency and repair of glycidol-induced DNA lesions

Aasa, J; Vare, D; Motwani, HV; Jenssen, D; Törnqvist, M
2016 | Mutat. Res. | 805 (38-45)

Glycidol (Gly) is an electrophilic low-molecular weight epoxide that is classified by IARC as probably carcinogenic to humans. Humans might be exposed to Gly from food, e.g. refined vegetable oils, where Gly has been found as a food process contaminant. It is therefore important to investigate and quantify the genotoxicity of Gly as a primary step towards cancer risk assessment of the human exposure. Here, quantification of the mutagenic potency expressed per dose (AUC: area under the concentration-time curve) of Gly has been performed in Chinese hamster ovary (CHO) cells, using the HPRT assay. The dose of Gly was estimated in the cell exposure medium by trapping Gly with a strong nucleophile, cob(I)alamin, to form stable cobalamin adducts for analysis by LC-MS/MS. Gly was stable in the exposure medium during the time for cell treatment, and thus the dose in vitro is the initial concentration×cell treatment time. Gly induced mutations in the hprt-gene at a rate of 0.08±0.01 mutations/10(5) cells/mMh. Through comparison with the effect of ionizing radiation in the same system a relative mutagenic potency of 9.5rad-eq./mMh was obtained, which could be used for comparison of genotoxicity of chemicals and between test systems and also in procedures for quantitative cancer risk assessment. Gly was shown to induce strand breaks, that were repaired by base excision repair. Furthermore, Gly-induced lesions, present during replication, were found to delay the replication fork elongation. From experiments with repair deficient cells, homologous recombination repair and the ERCC1-XPF complex were indicated to be recruited to support in the repair of the damage related to the stalled replication elongation. The type of DNA damage responsible for the mutagenic effect of Gly could not be concluded from the present study.

Interaction of benzo[a]pyrene diol epoxide isomers with human serum albumin: Site specific characterisation of adducts and associated kinetics

2016 | Sci Rep | 6:36243 (1-10)

Quantification of the mutagenic potency and repair of glycidol-induced DNA lesions

Aasa, J; Vare, D; Motwani, HV; Jenssen, D; Törnqvist, M
2016 | Mutat. Res. | 805 (38-45)

Characterization of a hemoglobin adduct from ethyl vinyl ketone detected in human blood samples

Carlsson, H; Motwani, HV; Osterman-Golkar, S; Törnqvist, M
2015 | Chem. Res. Toxicol. | 28 (2120-2129)

Mutagenicity and DNA repair of glycidol-induced adducts in mammalian cells and dose measurements using the cob(I)alamin trapping method

Aasa, J; Vare, D; Motwani, HV; Jenssen D; Törnqvist, M
2015 | Toxicol. Lett. | 238

Aspartic protease inhibitors containing tertiary alcohol transition-state mimics

Motwani, HV; De Rosa, M; Odell, LR; Hallberg, A; Larhed, M
2015 | Eur J Med Chem | 90 (462-490)

Alkylcobyrinate from sucralose and mechanistic aspects of its Co-C bond cleavage

Motwani, HV; Shimakoshi, H; Tornqvist, M; Golding, BT; Hisaeda, Y
2014 | Tetrahedron Lett. | 55 (2667-2670)

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

2014 | Toxicol. Appl. Pharmacol. | 281 (276-284)

Quantitative inter-species comparison approach of 1,3-butadiene metabolism based on in vitro enzyme kinetics using cob(I)alamin and in vivo AUC from haemoglobin adducts

2014 | Toxicol. Lett. | 229

Synthesis of P1 \’-Functionalized Macrocyclic Transition-State Mimicking HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol

De Rosa, M; Unge, J; Motwani, HV; Rosenquist, A; Vrang, L; Wallberg, H; Larhed, M
2014 | Eur J Med Chem | 57 (6444-6457)
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