CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study.

CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A->G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A->G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95% CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95% CI = 0.70-2.79) with OSCC.

CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study

CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A->G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A->G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95 percent CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95 percent CI = 0.70-2.79) with OSCC.

Medial septal area modulation of sustained negative shifts in awake rabbits.

Experiments were performed on rabbits with chronically implanted Ag-AgCl electrodes over occipital cortex and chrome-nickel stimulation electrodes in the medial septal area. Visual evoked potentials (VEP) were elicited by means of randomly occurring flashes. After measuring the N1-amplitude of the VEPs, responses with N1-1 amplitudes below a previously determined discriminative value were reinforced by a weak footshock 1.5 S1 after the flash. In the group of high-amplitude VEP we found longer negative shifts than in the group of low-amplitude VEP, starting 600-700 ms after flash and lasting up to the end of the observed time range. The stimulation of medial septal area (0.5 mA, 6 imp/s) during the normal flash application led to a delay of the maximum of this negative shift which returned now to baseline within the observed range. The amplitude of these sustained negative shifts was larger during septal stimulation. Larger negative shifts followed high-amplitude VEP than the low-amplitude ones. Repetition of usual flash application without septal stimulation after a 10 min break turned the negative shift to normal. After electrolytic destruction of medial septal area this late negative shift vanished without any restitution.

Activation state of the cortex could be changed by reinforcement of low-amplitude visual evoked potentials in rabbits.

Visually evoked potentials (VEP) were recorded chronically from occipital cortex in awake rabbits. The VEP typically consisted of a triphasic response (positive deflection P60--negative deflection N205--positive deflection P450) that was followed by a late negative shift starting about 750 ms after the eliciting flash. After computation of a discriminating amplitude value (200 or 250 microV) the VEP were divided for comparison in high- and low-amplitude groups. Significant differences between these groups existed in amplitudes and latencies of the early VEP components. High-amplitude VEP were followed by larger late negative shifts and had significantly (P less than 0.01) earlier second positive deflections. In these high-amplitude cases, the EEG-baseline was more negative than in the low-amplitude VEP. In addition, we found a more synchronized background EEG in the low-amplitude VEP group. We conclude that different VEP amplitudes depended on different activation states of the cortex which could be changed by reinforcement.

Activation-induced changes in evoked and slow brain potentials: effects of cocaine in awake rabbit.

To study the interrelations between event-related potentials and brain activation, evoked responses to visual stimulation registered from occipital cortex and hippocampal CA1 region were investigated in awake animals administered cocaine (2 mg/kg, SC) or saline. Administration of COCA resulted in longterm significant changes in heart and breathing rates and spontaneous EEG (desynchronization in the occipital cortex and slow rhythmic theta activity in the hippocampus), inhibition of animal responses to noxious electroshock stimuli and modification in different amplitudes of evoked responses (mainly in the cortex, the enhancement of negativity and bidirectional changes in late slow phase). Principally identical but more or less changes were observed in response to administration of saline. Obtained results are discussed in respect to their interrelations with the general activation organism's response and the modification of brain metabolism induced by cocaine in restrained rabbits.

An easy method to record slow potential shifts (SPS) in rabbits using the "oddball" paradigm.

Rabbits with chronically implanted Ag-AgCl electrodes over somatosensory and visual cortex were trained to a modified 'oddball' paradigm with visual stimulation. Event related potentials (ERP) and slow potential shifts (SPS) were recorded. By means of a computer controlled stimulator 'frequent' and 'rare' LED flashes were administered to the eyes of the rabbit. If 'rare' stimuli were reinforced by a weak electrical footshock, negative SPS rose steeper and reached significantly higher amplitudes than in 'frequent' conditions without reinforcement. Different kinds of the follow-up of 'frequent' and 'rare' series were tested. Best effects were obtained, if a session was divided into 3 blocks (3 srs. 'frequent'--5 srs. 'rare' reinforced--2 srs. 'frequent' and probability of 'rare' flashes was 20%. Our present data formed a basis for investigations on the neuronal and glial sources of SPS in rabbits.