Benzo(a)pyrene (BP), 2-hydroxybenzo(a)pyrene (2-HOBP), and 6-hydroxybenzo(a)pyrene (6-HOBP) were tested for tumorigenicity by i.p. injection into newborn mice. The mice were treated sequentially with 200, 400, and 800 nmol of compound on the first, eighth and fifteenth day of life, and the animals were killed at 24 weeks of age. Treatment with 2-HOBP caused about 4-fold more pulmonary tumors than BP, while 6-HOBP had little or no tumorigenic activity. Newborn mice treated with 2-HOBP, BP, and 6-HOBP had a 98, 81, and 11% incidence of pulmonary adenomas with an average of 24, 6.4, and 0.11 adenomas per mouse, respectively. In the control group, 7.5% of the animals had pulmonary adenomas with an average of 0.08 adenoma per mouse. When 25, 50, or 100 nmol of BP or 2-HOBP was applied to mouse skin once every 2 weeks for 60 weeks, both compounds had about the same carcinogenic activity. These results demonstrate the importance of evaluating the carcinogenic potential of chemicals in more than one tumor system. BP and 2-HOBP were tested for mutagenicity towards two strains of Salmonella typhimurium and towards Chinese hamster V79 cells in the presence of hepatic microsomes from rats pretreated with Aroclor 1254. The products formed during the metabolism of 2-HOBP or BP by liver microsomes had significant mutagenic activity.
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Alzheimers Dement
December 2024
University of Missouri, Columbia, MO, USA.
Background: Preclinical animal models are essential for the development of effective treatments. For instance, the 5xFAD mouse model successfully represents the pathophysiology of Alzheimer's disease (AD). Expression of humanized APP (K670N/M671L - Swedish, I716V - Florida, V717I - London) and PSEN1 (M146L and L286V), found in early onset AD patients, induces the production of amyloid-β 42 (Aβ42) and amyloid deposition, gliosis, and progressive neuronal loss.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Background: Recently, a highly significant brain proteome divergent modules change between Alzheimer's disease (AD) and CRND8 APP transgenic mice has been found. The M42 module is the module in human AD most highly correlated with amyloid and tau pathologies and cognitive decline. Among all proteins in this module, the (SPARC-related modular calcium-binding protein 1) SMOC1 is emerging as a robust biomarker of amyloid deposition in CSF.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester, Rochester, NY, USA.
Int J Dev Neurosci
February 2025
Department of Clinical Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Quercetin is a natural flavonoid and one of the most powerful antioxidants. Due to its wide range of biological properties, it may improve cognitive and physical performance by affecting nervous tissue. The current study is aimed at determining the effect of prenatal exposure to quercetin against methimazole (MMI)-induced hypothyroidism on reflexive motor behavior in mouse offspring.
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