Retinoblastoma protein regulates carcinogen susceptibility at heterochromatic cancer driver loci

Carcinogenic insult, such as UV light exposure, creates DNA lesions that evolve into mutations if left unrepaired. These resulting mutations can contribute to carcinogenesis and drive malignant phenotypes. Susceptibility to carcinogens (i.e., the propensity to form a carcinogen-induced DNA lesion) is regulated by both genetic and epigenetic factors. Importantly, carcinogen susceptibility is a critical contributor to cancer mutagenesis. It is known that mutations can be prevented by tumor suppressor regulation of DNA damage response pathways; however, their roles carcinogen susceptibility have not yet been reported. In this study, we reveal that the retinoblastoma (RB1) tumor suppressor regulates UV susceptibility across broad regions of the genome. In particular, centromere and telomere-proximal regions exhibit significant increases in UV lesion susceptibility when RB1 is deleted. Several cancer-related genes are located within genomic regions of increased susceptibility, including telomerase reverse transcriptase, TERT, thereby accelerating mutagenic potential in cancers with RB1 pathway alterations. These findings reveal novel genome stability mechanisms of a tumor suppressor and uncover new pathways to accumulate mutations during cancer evolution.

Antiproliferative, genotoxic and mutagenic potential of synthetic chocolate food flavoring

Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.

A comparison of mutagenic potential of Aji-no-Moto with a traditional chemical mutagen on microsporogenesis in barley (Hordeum vulagre L.)

Aji-no-Moto or Mono Sodium Glutamate (MSG) is a flavour enhancer being used extensively in South East Asian cuisine. The Federation of American Societies for Experimental Biology for the United States Food and Drug Administration (FDA) has concluded that MSG is safe when "eaten at customary levels" but there is still great confusion regarding its toxicity at higher concentrations. Therefore, it was decided to assess the mutagenic efficacy of MSG on a plant system and present the findings as a model for probably similar effects in the animal model. For this, a traditionally popular genus for genetic studies, Hordeum vulgare L. or winter barley, was used as the model system. The studies of microsporogenesis were done in order to see the long term effect. The sets were compared with experimental sets of plants grown from seeds treated with a traditional chemical mutagen Ethyl Methane Sulphonate (EMS). The study revealed that MSG does not induce much genotoxic effects at lower doses and the chromosomal damages induced were very few. However, at higher doses, it almost equals the effects of EMS in terms of heritable genetic damage. The work is significant as MSG continues to be one of the most popular flavouring agents and does not face any challenge to its biosafe status. However, the clastogenic and chromotoxic effects of higher doses of MSG as observed in the study are in total contradiction to the popular belief.

H2A.X Phosphorylation in Oxidative Stress and Risk Assessment in Plasma Medicine

At serine139-phosphorylated gamma histone H2A.X (γH2A.X) has been established over the decades as sensitive evidence of radiation-induced DNA damage, especially DNA double-strand breaks (DSBs) in radiation biology. Therefore, γH2A.X has been considered a suitable marker for biomedical applications and a general indicator of direct DNA damage with other therapeutic agents, such as cold physical plasma. Medical plasma technology generates a partially ionized gas releasing a plethora of reactive oxygen and nitrogen species (ROS) simultaneously that have been used for therapeutic purposes such as wound healing and cancer treatment. The quantification of γH2A.X as a surrogate parameter of direct DNA damage has often been used to assess genotoxicity in plasma-treated cells, whereas no sustainable mutagenic potential of the medical plasma treatment could be identified despite H2A.X phosphorylation. However, phosphorylated H2A.X occurs during apoptosis, which is associated with exposure to cold plasma and ROS. This review summarizes the current understanding of γH2A.X induction and function in oxidative stress in general and plasma medicine in particular. Due to the progress towards understanding the mechanisms of H2A.X phosphorylation in the absence of DSB and ROS, observations of γH2A.X in medical fields should be carefully interpreted.

Effects of Prenatal Exposure to Aflatoxin B1: A Review

Aflatoxins are mycotoxins produced as secondary fungal metabolites. Among them, aflatoxin B1 (AFB1) stands out due to its genotoxic and mutagenic potential, being a potent initiator of carcinogenesis. In this review, the outcomes from the published literature in the past 10 years on the effects of AFB1 pathophysiological mechanisms on embryological and fetal development are discussed. In several animal species, including humans, AFB1 has a teratogenic effect, resulting in bone malformations, visceral anomalies, lesions in several organs, and behavioral and reproductive changes, in addition to low birth weight. The mutagenic capacity of AFB1 in prenatal life is greater than in adults, indicating that when exposure occurs in the womb, the risk of the development of neoplasms is higher. Studies conducted in humans indicate that the exposure to this mycotoxin during pregnancy is associated with low birth weight, decreased head circumference, and DNA hypermethylation. However, as the actual impacts on humans are still unclear, the importance of this issue cannot be overemphasized and studies on the matter are essential.

Evaluation Of The Mutagenic Potential Of The Polyphenol Extract From Blueberries In The Ames Test

In this research, mutagenic properties of blueberry polyphenol extract were studied in gene mutation induction test (Ames test) on four strains of Salmonella typhimurium TA98, TA100, TA1535, TA1537. None of the strains of Salmonella typhimurium showed statistically reliable dose-dependent increase in number of revertant colonies in the presence of investigated drug in the studied dose range from 4,0 to 40,0 mg/ml relative to baseline of spontaneous mutations. The blueberry extract does not have any mutagenic activity in the researched dose range in relation to TA98, TA100, TA1535, TA1537 strains of Salmonella typhimurium.