Chromosome aberrations products

Literature reports iadicate that sodium sorbate causes weak genotoxic effects such as chromosomal aberrations and mutations ia mammalian cells (172,173). This effect is thought to be caused by oxidative products of sodium sorbate ia stored solutions (173—175). The main oxidation product of sodium sorbate, 4,5-oxohexenoate, is mutagenic ia a Salmonella mammahan-microsome test (176). Sorbic acid and potassium sorbate were not genotoxic under the same test procedures (167,172,174—177). 

There are several reports of noteworthy extrapulmonary effects in laboratory animals with concentrations of about 0.2 ppm. These include reduced voluntary activity, chromosomal aberrations in circulating lymphocytes of hamsters, increased neonatal mortality, and greater incidence of jaw abnormalities in offspring of ozone-exposed mice. The mechanisms of these reported effects and whether th are due to direct actions of absorbed ozone, some secondary reaction product, or secondary responses to the stress of local actions in the lung are largely unknown. However, reported analogous effects in humans exposed to ozone, such as changes in visual acuity and headache (possibly related to the reduced activity in... 

In genotoxic assays, significant increases in frequencies of chromosomal aberrations in peripheral lymphocytes have been reported in uranium miners. This effect has been attributed to radon daughter products and more recently to mutagenic mycotoxins produced by molds present in the uranium mines."... 

Bird. R.P.. Draper. H.H. Basrur, PK. (1982) Effect of malonaldehyde and acetaldehyde on cultured mammalian cells production of micronuclei and chromosomal aberrations. Mutat. Res.. 101. 237-246... 

Natarajan, A.T., Simons, J.W.I.M., Vogel, E.W. van Zeeland, A.A. (1984) Relationship between cell killing, chromosomal aberrations, sister-chromatid exchanges and point mutations induced by monofunctional alkylating agents in Chinese hamster cells. A correlation with different ethylation products in DNA. Mutat. Res., 128, 31-40... 

In lymphocytes obtained from six workers employed in 1,4-dioxane production and exposed to unspecified airborne levels of the compound for 6-15 years, no increase in chromosomal aberrations was found relative to that observed in an equal number of controls (Thiess etal., 1996). 

The genetic activity of pure synthetic Maillard products has also been studied. 2-Methylpyrazine, 2-ethylpyrazine, 2,5-di-methylpyrazine and 2,6-dimethylpyrazine all induced a significant increase in chromosome aberrations in Chinese hamster ovary cells... 

SCE production is probably caused by S-phase-dependent chemicals. Consequently, DNA repair phenomena that remove lesions from DNA before lymphocytes cure stimulated to enter the S phase can influence the yield of SCEs just as they can influence the yield of chromosomal aberrations. Thus, DNA repair processes and other factors that influence SCE production still make the mechanistic interpretation of SCE production complicated when one is monitoring human populations for small exposure to chemicals.230... 

Countryman, P.I., and J.A. Heddle. The production of micronuclei from chromosome aberrations in irradiated cultures of human lymphocytes. Mutat. Res. 41 321-332, 1976. 

Kihlman, B. A. 1964. The production of chromosomal aberrations by streptonogrin in vicia faba. Mutation Research 1 54-62. 

Scott, D, and H. J. Evans. 1964. On the non-requirement for deoxyribonucleic acid synthesis in the production of chromosome aberrations by 8-ethoxycaffeine. Mutation Research 1 146-156. 

In general, genotoxicity standard assays (e.g., bacterial reverse mutation assay [Ames test], in vitro chromosomal aberration assay, mouse lymphoma gene mutation assay, and rodent micronucleus assay) may not be suitable assays because the test cells do not contain the appropriate receptors to transport the product (i.e.,not a relevant species) or because the biopharmaceutical... 

Twenty-seven out of 44 FDA-approved biopharmaceuticals have been tested in a battery of genotoxicity assays. Eighty-five different assays performed yielded negative results. The most commonly performed assays were the Ames test, the chromosomal aberration assay in human lymphocytes, the mouse lymphoma gene mutation assay, and the mammalian in vivo erythrocyte micronucleus test. Examples of the range of biopharmaceutical products tested include, domase alfa (deoxyribonuclease I-DNAse), trastuzumab (mAb to human epidermal growth factor receptor 2), alteplase (tissue plasminogen activator), infliximab (mAb to the human tumor necrosis factor a). 

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