geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Safety assessment for non-genotoxic rodent carcinogens: curves, low-dose extrapolations, and mechanisms in carcinogenesis


, : Safety assessment for non-genotoxic rodent carcinogens: curves, low-dose extrapolations, and mechanisms in carcinogenesis. Human & Experimental Toxicology 19(10): 557-60; Discussion 571-2

The most frequent biologic events associated with multispecies multisite rodent non-genotoxic carcinogenesis include robust liver P450 enzyme induction without liver toxicity. This cancer process is not relevant for humans as exemplified by phenobarbital. A host of other pharmaceuticals, including loratidine and atorvastatin, with current sales in the billions of dollars attests to the lack of relevance of our rodent models acting via this specific process. Hopefully, the mechanism of phenobarbital will no longer draw research money in further probing the irrelevant in human carcinogenesis. The known human carcinogens not linked with genetic injury all perturb tissue growth/replication in humans as well as in rodent short-term tests at doses ultimately linked with cancer. Clearly identifying exposures perturbing growth/replication versus exposures not perturbing growth provides an effective tool for demonstrating the threshold for cancer risk in refining the risk assessment as capably described by Dr. Klaunig. Hopefully, we can begin to increasingly use data-based decisions in risk assessment versus hypothetical low- dose extrapolations and mathematical modeling, building on the wealth of current understanding in human and rodent cancer processes in arenas beyond pharmaceutics.

US$29.90

PMID: 11211992


Other references

Grenier, J.K.; Foureman, P.A.; Sloma, E.A.; Miller, A.D., 2017: RNA-seq transcriptome analysis of formalin fixed, paraffin-embedded canine meningioma. Meningiomas are the most commonly reported primary intracranial tumor in dogs and humans and between the two species there are similarities in histology and biologic behavior. Due to these similarities, dogs have been proposed as models for mening...

Malkov, I.S.; Shakirov, M., I.; Nizamutdinov, E.Z.; Garaev, V.N.; Kozlov, R.K., 2006: Intraoperation prophylaxis of pyo-inflammatory complications of wounds. With the aim of increasing effectiveness of apparatus surgical wounds' correction by means of evenly distributed tension of tissues without local circulation impairment the compensating device has been developed. 36 patients with acute surgic...

Park, H.; Tan, C.C.; Faulkner, A.; Jabbar, S.B.; Schmid, G.; Abey, J.; Iuvone, P.Michael.; Pardue, M.T., 2014: Retinal degeneration increases susceptibility to myopia in mice. Retinal diseases are often associated with refractive errors, suggesting the importance of normal retinal signaling during emmetropization. For instance, retinitis pigmentosa, a disease characterized by severe photoreceptor degeneration, is associ...

Dir, R.S.; Zell, S.C., 1998: Triple drug therapy versus select use of dual nucleoside analogs as front line antiretroviral treatment A cost comparison. Journal of Investigative Medicine 46(1): 100A, Jan

Barchuk, A.S.; Cheremnykh, A.A.; Keller, I.M., 1970: Primary lymphogranulomatosis of the lung (l case). Voprosy Onkologii 16(2): 82-85

Stone, R., 2010: Ecology. Severe drought puts spotlight on Chinese dams. Science 327(5971): 1311-1311

Borges, R.M., 2008: Commentary: The objection is sustained: a defence of the defense of beanbag genetics. International Journal of Epidemiology 37(3): 451-454

Stepanovic, I., 1961: Pseudo-exfoliation of the lenticular capsule and its clinical significance. Srpski Arhiv Za Celokupno Lekarstvo 89: 1471-1476

Kordus V.I.; Motovilov P.I., 1989: The geochemical nature and formation conditions of highly paraffinous oils. Ultracompressed gases, under conditions of high pressures and temperatures, dissolve oils to produce supercritical gas condensate and oil system. The system migrates and undergoes retrograde condensation to form multihorizon oil and gas fields. Hi...

Gray, P.A.; Keith, J., 1988: The application of a spreadsheet formatting procedure in the development and implementation of a habitat evaluation model for the Northwest Territories. Preliminary results are given from use of the model to evaluate habitat for Alces alces. The advantages and applicability of a commercially-available spreadsheet program are discussed.