Environmental toxicants such as chemicals, heavy metals, and pesticides have been shown to promote transgenerational inheritance of abnormal phenotypes and/or diseases to multiple subsequent generations following parental and/ or ancestral exposures. This study was designed to examine the potential transgenerational action of the environmental toxicant trichloroethane (TCE) on transmission of liver abnormality, and to elucidate the molecular etiology of hepatocyte cell damage. A total of thirty two healthy immature female albino mice were randomly divided into three equal groups as follows: a sham group, which did not receive any treatment; a vehicle group, which received corn oil alone, and TCE treated group (3 weeks, 100 μg/kg i.p., every 4th day). The F0 and F1 generation control and TCE populations were sacrificed at the age of four months, and various abnormalities histpathologically investigated. Cell death and oxidative stress indices were also measured. The present study provides experimental evidence for the inheritance of environmentally induced liver abnormalities in mice. The results of this study show that exposure to the TCE promoted adult onset liver abnormalities in F0 female mice as well as unexposed F1 generation offspring. It is the first study to report a transgenerational liver abnormalities in the F1 generation mice through maternal line prior to gestation. This finding was based on careful evaluation of liver histopathological abnormalities, apoptosis of hepatocytes, and measurements of oxidative stress biomarkers (lipid peroxidation, protein carbonylation, and nitric oxide) in control and TCE populations. There was an increase in liver histopathological abnormalities, cell death, and oxidative lipid damage in F0 and F1 hepatic tissues of TCE treated group. In conclusion, this study showed that the biological and health impacts of environmental toxicant TCE do not end in maternal adults, but are passed on to offspring generations. Hence, linking observed liver abnormality in the offspring to environmental exposure of their parental line. This study also illustrated that oxidative stress and apoptosis appear to be a molecular component of the hepatocyte cell injury.
Mohamed A. Al-Griw , Soad A. Treesh, Rabia O. Alghazeer, Sassia O. Regeai (7-2017)

Alterations in genes encoding the xenobiotic-metabolizing enzymes contribute to the variability in susceptibility to various cancers. In this study, we assessed the possible association between the CYP1A1 variants and lung cancer (LC) risk in a population of Libyan males. For this study, we selected 20 unrelated healthy controls and 32 patients with LC. DNA samples from the controls and patients were screened by DNA-PCR and direct DNA sequence analysis to search for genetic sequence variations in CYP1A1 gene (exon 7 and 3’ non-coding region). CYP1A1 mutations were identified in 11.5 % adult subjects and cases analyzed, and all were males. Overall, 11 CYP1A1 mutations were documented in this study implicating exon 7 and 3’ non-coding region. Nonsense, missense, and frame-shift mutations accounted for, respectively, 27.3 %, 63.6 % and 9.1 % of all CYP1A1 mutations. Three missense mutations namely CYP1A1*2B/m2 (rs1048943), CYP1A1*4/m4 (rs1799814), and CYP1A1*2A/m1 (rs4646903) have already been reported. The remaining mutations have not been described previously. We observed two apparently heterozygous carriers of mutation CYP1A1*2B/m2 (CYP1A1 4889A/G [642Ile/Val] genotype) in control group. We also observed two heterozygotic genotypes one containing mutation m4 (CYP1A1 4887C/A [461Thr/Asp]) and another containing mutation m1 (6235T/C) in cancer group. The mutations m2, m4, and m1 accounted for, respectively, 18.2 %, 9.1 % and 9.1 % of all CYP1A1 mutations. Comparing the clinical features showed that PLT and WBC counts were lower in CYP1A1 mutant than in CYP1A1 wild type, but they have not reached statistical significant (P > 0.05). The average age of CYP1A1 mutant was lower than in CYP1A1 wild type. Overall, these findings suggest that genetic alterations in the metabolic gene CYP1A1 are too rare to be of clinical relevance in this study, implying different pathways for the LC risk with respect to CYP1A1 polymorphisms as a risk factor for LC at least in this study.
Najah A. Fares, Othman A. El-Ansari, Mohamed A. Al-Griw(4-2017)

Alkaline phosphatase (ALP) enzyme level, which is routinely measured at clinical laboratories, increases in end-stage renal disease (ESRD) and hepatitis patients. This study investigated the difference in ALP level among ESRD and hepatitis patients. ALP level was measured in sera of patients suffering from ESRD, HCV and HBV infections, as well as patients suffering from comorbidity of these diseases, then the obtained values of ALP level were statistically compared to a control group. The results of three-Way ANOVA revealed that the mean of ALP level increased significantly (P-value< 0.05) in all types of diseases compared to the control group, with the highest increase in case of ESRD patients infected with Hepatitis B and C. Also, it was found that the interaction of group-gender significantly (P-value< 0.05) altered ALP level in patients suffering from HCV or HBV infections, while the interaction of group-age, gender-age, group-gender-age were found not to significantly alter it. In conclusion, ESRD patients with HBV/HCV coinfection may have a higher risk of liver-related morbidity and mortality than ESRD or HBV or HCV patients. arabic 25 English 103
HA Alemam, A Bashein(1-2020)