Involvement of p53 function in different magnitude of genotoxic and cytotoxic responses in in vitro micronucleus assays

Cytotoxicity and Genotoxicity of Panel of Single- and Multiwalled Carbon Nanotubes:In VitroEffects on Normal Syrian Hamster Embryo and Immortalized V79 Hamster Lung Cells

“…However, even if V79 cells do have a mutated p53 gene, we showed in the present study that CNTs induced the same cytotoxicity and induced micronucleated cell formation in both cell types. These findings corroborate those of Hashimoto et al [ 69 ], who found no difference in sensitivity to micronucleus induction and cytotoxicity in p53-wild and p53-null human lymphoblastoid cells. Furthermore, the mitotic index suggests that a cell cycle arrest occurs in both cell types following exposure to CNTs.…”

Relationships between p53 status, apoptosis and induction of micronuclei in different human and mouse cell lines in vitro: Implications for improving existing assays

“…The data generated suggest that these differences between human and rodent cell lines was not primarily due to the p53 status of the cell, but more likely to some element(s) of species difference (DNA repair capability, cell cycle control etc. ), that have been alluded to in earlier published work [8]. This was also consistent with observations of Honma and Hayashi [36] for the micronucleus endpoint where little to no differences in response between p53 deficient WTK-1 and p53 proficient TK6 cells (human cells) were observed when looking at a variety of clastogens and spindle poisons.…”

“…As such, for these data there seemed questionable impact of p53 status of the cell in contrast to the early hypothesis of Fowler et al [2] comparing p53 proficient human with p53 deficient hamster cell lines. This is supported from work conducted by Hashimoto et al [8] and Honma and Hayashi [36], who compared the micronucleus and cytotoxicity responses between human TK6, human NH32 (P53 knock-out) and CHL (hamster mutant p53) cells treated with a range of chemicals with differing modes of action. The data from these trials also indicated a similarity of response between the p53 knock-out NH32 cells and TK6 cells such that p53 status could not account for the differing sensitivity to MN induction or cytotoxicity between CHL and TK6 cells.…”

“…Should the damage be too severe, cells may undergo apoptosis. In mammalian cells the tumour suppressor gene (p53) plays a key role in safeguarding the integrity of the human genome via modulating cell cycle arrest, DNA repair, and apoptotic processes [7,8].…”

Genotoxic mixtures and dissimilar action: concepts for prediction and assessment

“…This line of argument is no doubt relevant in the context of discussions about extrapolations in a risk assessment and regulatory context, but does not invalidate our observations. It is conceivable that differences in p53 status have an impact on differences in the sensitivity of cells to MN-inducing agents, although evidence from experiments with p53 deficient variants of human TK6 cells have revealed little influence of p53 status on MN formation (Hashimoto et al 2011; Honma and Hayashi 2011). Furthermore, deviations from additivity for the combined effects of gamma irradiation and ethyl methanesulfonate seemed to be species specific rather than dependent on p53 status (Lutz et al 2002).…”