Biomedical subjects

P Pani

Publications and source records attributed to P Pani.

At least 19 recordsLinked to original sources

PubMed2001

A growth-constrained environment drives tumor progression invivo.

We recently have shown that selective growth of transplanted normal hepatocytes can be achieved in a setting of cell cycle block of endogenous parenchymal cells. Thus, massive proliferation of donor-derived normal hepatocytes was observed in the liver of rats previously given retrorsine (RS), a naturally occurring alkaloid that blocks proliferation of resident liver cells. In the present study, the fate of nodular hepatocytes transplanted into RS-treated or normal syngeneic recipients was followed. The dipeptidyl peptidase type IV-deficient (DPPIV(-)) rat model for hepatocyte transplantation was used to distinguish donor-derived cells from recipient cells. Hepatocyte nodules were chemically induced in Fischer 344, DPPIV(+) rats; livers were then perfused and larger (>5 mm) nodules were separated from surrounding tissue. Cells isolated from either tissue were then injected into normal or RS-treated DPPIV(-) recipients. One month after transplantation, grossly visible nodules (2--3 mm) were seen in RS-treated recipients transplanted with nodular cells. They grew rapidly, occupying 80--90% of the host liver at 2 months, and progressed to hepatocellular carcinoma within 4 months. By contrast, no liver nodules developed within 6 months when nodular hepatocytes were injected into the liver of recipients not exposed to RS, although small clusters of donor-derived cells were present in these animals. Taken together, these results directly point to a fundamental role played by the host environment in modulating the growth and the progression rate of altered cells during carcinogenesis. In particular, they indicate that conditions associated with growth constraint of the host tissue can drive tumor progression in vivo.

Animals↗

PubMed2001

Massive liver replacement by transplanted hepatocytes in the absence of exogenous growth stimuli in rats treated with retrorsine.

A strategy for hepatocyte transplantation was recently developed whereby massive replacement of the recipient liver is achieved after a combined treatment with retrorsine, a pyrrolizidine alkaloid, and partial hepatectomy. We now investigated whether liver repopulation could occur in this animal model in the absence of any exogenous growth stimuli (eg, partial hepatectomy) for the transplanted cells. Dipeptidyl-peptidase type IV-deficient (DPPIV-) rats were used as recipients. Rats were given two injections of retrorsine (30 mg/kg each, 2 weeks apart), followed by transplantation of 2 x 10(6) hepatocytes isolated from a normal, syngeneic, DPPIV+ donor. At 2 weeks after transplantation, clusters of DPPIV+ hepatocytes occupied 3.3 +/- 0.9% of host liver, increasing to 38.2 +/- 6.3% at 2 months, and to 65.9 +/- 8.8% at 5 months. By 1 year, >95% of the original hepatocytes were replaced by donor-derived cells. Serum parameters related both to hepatocyte function and integrity (including glucose, bilirubin, total proteins, cholinesterase, alanine aminotransferase, and alkaline phosphatase) were in the normal range in retrorsine-treated and repopulated animals. These results provide further insights toward developing strategies for effective liver repopulation by transplanted hepatocytes with reduced toxicity for the host and potential clinical applicability.

Animals↗

PubMed2001

One-step detection and genotyping of human papillomavirus in cervical samples by reverse hybridization.

This study describes a nonisotopic polymerase chain reaction-reverse hybridization-based method (PCR-RH) for the one-step detection and genotyping of anogenital human papillomavirus (HPV) in a microwell format. HPV DNA was amplified and labeled by PCR using GP5+/GP6+ primers. Labeled amplicons were hybridized to 20 HPV type-specific capture probes anchored to the surface of plastic microwells and detected by an immunoenzymatic assay. Assay sensitivity was <50 pg labeled amplicon, and no cross-reactivity was observed, as determined by hybridizing serial dilutions of labeled PCR products to either matched or mismatched capture probes. The assay was tested on 66 clinical samples (23 specimens with normal histology, I fibropapilloma, 26 cervical intraepithelial neoplasia grade 1 [CIN1], 9 CIN2, and 7 CIN3) and compared with a method based on restriction fragment length polymorphism (RFLP) of PCR products. PCR-RH and PCR-RFLP performed equally well on clinical samples. The overall HPV detection rate was similar: 65.1% (43/66) for PCR-RH and 57.6% (38/66) for PCR-RFLP. HPV DNA was found in all CIN2 and CIN3 samples by both methods; however, PCR-RH detected more positives among normal biopsy samples and CINI cases. Overall, there was good agreement between the two genotyping methods, but RH yielded fewer cases with undetermined HPV genotype.

Consensus Sequence↗

PubMed2000

Early exposure to restraint stress enhances chemical carcinogenesis in rat liver.

This study examines the effect of a stress-associated condition on chemical hepatocarcinogenesis in the rat. Rats were given diethylnitrosamine (200 mg/kg. b.w., i.p.), followed, 1 week later, by three cycles of immobilization at room temperature. Two weeks after the last cycle they were treated according to the resistant hepatocyte protocol. At 4 weeks after selection, mean size of glutathione-S-transferase 7-7 positive foci/nodules was increased in the immobilized group (0.82+/-0.22 vs. 0.25+/-0.04 mm(2) in controls). Furthermore, at the end of 1 year 10/13 animals (77%) developed hepatocellular carcinoma in the former group, while only 6/14 (43%) incidence of cancer was found in controls. These results indicate that exposure to restraint stress early during carcinogenesis enhances the development of chemically-induced hepatocellular carcinoma in the rat.

Animals↗

PubMed2000

The resistance phenotype in the development and treatment of cancer.

Phenotypic resistance, acquired early in carcinogenesis, has an established role in the pathogenesis of cancer in well-characterised experimental systems, and possibly also has a role in the origin of human cancer. It has been suggested that sunlight, an established risk factor for human skin carcinogenesis, is able to induce rare altered cells resistant to toxicity and to favour their clonal expansion via toxic effects exerted on normal keratinocytes. Other major risk factors for human neoplasia, including smoking and ageing, may also act partly through imposition of a constrained growth environment in the target organ to favour the emergence of altered resistant cells. Strategies aimed at counteracting this constrained environment could be effective in attenuating the force that sustains clonal expansion of altered cells.

Animals↗

PubMed2000

[Detection and genetic typing of human papillomaviruses in cervical biopsies in Cagliari Province].

INTRODUCTION: Human Papillomavirus (HPV) infection is considered an important risk factor for the development of cervical carcinoma. The aim of this work was to detect and genotype HPV DNA in cervical lesions from our Province. METHODS: HPV DNA was amplified by polymerase chain reaction (PCR) and genotyped by restriction fragment length polymorphism (RFLP) analysis. A total of 101 biopsies (43 koilocytic atypias, 20 CIN1, 19 CIN2, 17 CIN3 and 2 squamous carcinomas) were analyzed. RESULTS: HPV DNA was found in 41.8% of koilocytic atypias, in 95.0% of CIN1 and 100% of CIN2 and higher grade lesions. Only high risk genotypes were found in CIN2-3 and invasive carcinomas. HPV 16 was the most prevalent type in both CIN1 and CIN2-3 and the only HPV type found in situ and invasive carcinomas. HPV type 51 was found in 21.0% of CIN1 but it was rare in CIN2 and absent in more advanced lesions.

Adult↗

PubMed2000

[Simultaneous detection and typing of human papillomavirus in cervical biopsies using PCR-reverse hybridization].

INTRODUCTION: Genotyping of Human papillomavirus (HPV) is an important step in the clinical evaluation of the oncogenic risk associated with HPV infection of cervical mucosa. The purpose of this work was to develop a fast PCR-reverse-hybridization assay (PCR-RH) for the simultaneous detection and genotyping of anogenital HPVs. METHODS: HPV DNA from cervical biopsies was amplified by consensus primer-PCR. Digoxigenin-labeled PCR products were hybridized to type-specific probes anchored to the surface of plastic microwells and revealed by an ELISA system. RESULTS: The method was tested on 115 clinical samples (81 koilocytic atypias, 11 CIN1, 10 CIN2, 12 CIN3 and 1 squamous carcinoma). HPV DNA was found in 56.7% koilocytic atypias, in 90.9% of CIN1 and in 100% of CIN2 and higher-grade lesions. Thus, PCR-RH is sensitive, rapid, easy-to-perform and readily applicable to the routine analysis of a large number of samples.

Biopsy↗

PubMed1999

Direct hyperplasia does not enhance the kinetics of liver repopulation in a new model of hepatocyte transplantation in the rat.

BACKGROUND/AIMS: We have recently developed a new model of extensive liver repopulation by transplanted hepatocytes following exposure to pyrrolizidine alkaloids. In the present study, the effect of 2/3 partial hepatectomy (PH) and that of a potent direct liver mitogen, lead nitrate, were compared in their ability to modulate the kinetics of liver repopulation. METHODS: Fischer 344 rats deficient in enzymatic activity for dipeptidyl-peptidase IV (DPPIV-) were used as cell transplantation recipients. They were given 2 doses of the pyrrolizidine alkaloid retrorsine (30 mg/kg, i.p.), 2 weeks apart, followed 2 weeks later by transplantation of 2 x 10(6) hepatocytes (via the portal vein), freshly isolated from a normal congeneic DPPIV+ donor. PH was carried out or a single injection of lead nitrate (100 micromol/kg, i.v.) was administered 2 weeks post-transplantation. Liver samples obtained at different time points post-treatment were processed histochemically for DPPIV activity. RESULTS: The percent of liver sections occupied by DPPIV+ hepatocytes was <1% at the time of PH or lead nitrate administration. In animals which underwent PH, it increased to 33.4+/-5.7% at 2 weeks and to 55.6+/-8.5% at 1 month. However, in animals receiving lead nitrate, these percentages were only 3.3+/-1.3% at 2 weeks and 16.2+/-3.9% at 1 month. Repeated injections of lead nitrate had no additional effect. Further experiments indicated that an acute mitogenic response to lead nitrate was present in transplanted cells, while resident hepatocytes were inhibited by retrorsine. CONCLUSIONS: These results indicate that direct mitogenic signals (such as those induced by lead nitrate), and compensatory signals (such as those elicited by PH), are not equally effective on kinetics of liver repopulation in this system. The possible reasons for these differential effects are discussed.

Animals↗

PubMed1999

Liver regeneration in response to partial hepatectomy in rats treated with retrorsine: a kinetic study.

BACKGROUND/AIM: We have designed an experimental model in which transplantation of normal hepatocytes into rats previously treated with retrorsine (a naturally-occurring pyrrolizidine alkaloid) results in near-complete replacement of the recipient liver by donor-derived cells. Two/thirds partial hepatectomy was found to be essential for this process to occur. To probe this finding, in the present study we describe the kinetics of liver regeneration in response to partial hepatectomy in rats given retrorsine. METHODS: Six-weeks-old male Fisher 344 rats received retrorsine (2 injections of 30 mg/kg each, i.p., 2 weeks apart), or the vehicle. Four weeks after the last injection, partial hepatectomy was performed and rats were killed at 1, 2, 3, 6, and 15 days thereafter. RESULTS: At time zero, i.e. prior to partial hepatectomy, liver weight and total liver DNA content were significantly lower in retrorsine-treated animals compared to controls (DNA content: 19.2+/-1.7 vs. 25.7+/-1.1 mg/liver). Diffuse megalocytosis (enlarged hepatocytes) was present in the group exposed to retrorsine. By day 3 post-partial hepatectomy liver DNA content in control animals had more than doubled compared to day 1 values (20.2+/-1.5 vs. 8.8+/-1.2), while very little increase was seen in retrorsine-treated rats at the same time points (7.6+/-0.4 vs. 6.1+/-0.2). At 2 weeks after partial hepatectomy, total DNA content returned close to normal levels in the control group (26.9+/-1.0 mg/liver); however, the value was still very low in animals receiving retrorsine (9.1+/-0.7). Data on BrdU labeling were consistent with this pattern and indicated that DNA synthesis following partial hepatectomy was largely inhibited in the retrorsine group. Similarly, no mitotic response was observed in hepatocytes following partial hepatectomy in animals exposed to retrorsine. CONCLUSIONS: These results clearly indicate that retrorsine exerts a strong and persistent cell cycle block on hepatocyte proliferation. Further, these results are in agreement with the hypothesis that selective proliferation of transplanted hepatocytes in retrorsine-treated animals is dependent, at least in part, on the persistent cell cycle block imposed by the alkaloid on endogenous parenchymal cells.

Animals↗

PubMed1999

Effect of fasting/refeeding on the incidence of chemically induced hepatocellular carcinoma in the rat.

Caloric restriction has been associated with a delay in the development of both spontaneous and induced neoplasia. In contrast, cycles of fasting/refeeding were shown by us and others to enhance the incidence of early lesions during chemical carcinogenesis in rat liver. The present, long-term study was undertaken to establish whether such a diffential effect would also extend to the later phases of cancer development, until the overt appearance of neoplasia. Male Fischer 344 rats were initiated with a single dose of diethylnitrosamine (DENA, 200 mg/kg i.p.) and starting 1 week later they were either exposed to three cycles of fasting (3 days) followed by refeeding (11 days) or were fed continuously. Seven weeks after DENA administration the rats were exposed to the resistant hepatocyte model of the liver tumor promotion protocol. All animals were killed 1 year after initiation. Incidence of hepatocellular carcinoma was 2-fold higher in the fasted/refed group compared with the controls (72 versus 36%). In addition, cancers were also larger and of higher histological grade in the former group, with one animal showing metastases to the lungs, while no metastases developed in control animals. Fasting caused a decrease in total liver DNA (from 25.2 +/- 1.1 to 16.5 +/- 1.1 mg after 3 days) which was associated with a decrease in hepatocyte labeling index and mitotic activity and high levels of single cell death (apoptosis). In contrast, a sharp increase in hepatocyte proliferation was observed on day 2 of refeeding and this was more pronounced in glutathione S-transferase 7-7 positive foci compared with surrounding liver (10.2 +/- 2.3 versus 4.6 +/- 0.8%). Such a proliferative wave was associated with a sharp decline in the incidence of cell death. It is concluded that fasting/refeeding performed early after initiation accelerates the development of chemically induced hepatocellular carcinoma in the rat.

Animals↗

PubMed1999

Alterations of lipid and cholesterol metabolism in cachectic tumor-bearing rats are prevented by insulin.

The ascites hepatoma Yoshida AH130 causes in the host a rapid and progressive body weight loss, associated with reduced food intake, and protein and lipid hypercatabolism. Because insulin regulates glucose as well as lipid and protein metabolism, we suggest that the observed alterations are at least in part secondary to hypoinsulinemia and/or to the increase of counterregulatory hormones in AH130-bearing rats. To verify this hypothesis, controls with free access to food (n = 4), controls with free access to food plus insulin (107 micromol. kg body wt-1. d-1) (n = 4), controls pair-fed to the tumor-bearing rats (n = 4), pair-fed controls treated with insulin (n= 4), tumor hosts (n = 9), and tumor hosts treated with insulin (n = 6) were used. The Yoshida ascites hepatoma cells ( approximately 10(8) cells/rat) were inoculated intraperitoneally. Daily food intake and body weight were measured; insulin was injected starting the day of tumor implantation for 6 d. The metabolism of both cholesterol and lipids was investigated in tumor cells, and ascitic fluid and blood serum were investigated at the end of treatment. Insulin prevented the reduction of food intake (19 +/- 0.6 vs. 13 +/- 0.4 g/d, P < 0.01; AH130 hosts treated and not treated with insulin, respectively), the loss of body weight (202 +/- 12 vs. 135 +/- 9 g, P < 0.01), lowered the circulating triglycerides (48.3 +/- 4.9 vs. 84.5 +/- 7.1 mmol/L, P < 0.01), and free fatty acids (561 +/- 47 vs. 989 +/- 54 mmol/L (P < 0.01), while corrected the decrease of adipose lipoprotein lipase activity (1,240 +/- vs. 300 +/- pmol FA, P < 0.01) observed in AH130 hosts. Moreover, insulin prevented the decrease in HDL cholesterol (13.2 +/- 0.8 vs. 9.3. +/- 0.7 mmol/L, P < 0.01) and significantly increased hepatic cholesterol synthesis as evaluated by 14C-acetate incorporation into cholesterol, in both liver (3,337 +/- 245 vs. 830 +/- 115 Bq/g, P < 0.01) and AH130 cells (11,676 +/- 1,693 vs. 4,196 +/- 527 Bq/10(6) cells, P < 0.01). Thus insulin treatment ameliorated many metabolic derangements, with a lengthening of rats survival time (7 +/- 1 vs. 11 +/- 1 d, P < 0.05) without significantly stimulating tumor growth. These data, together with our previous observations on the effectiveness of insulin on protein turnover perturbations, suggest that many metabolic alterations occurring during cancer cachexia can be avoided by the administration of this hormone.

Animals↗

PubMed1998

Long-term, near-total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine.

Genetically marked hepatocytes from dipeptidyl peptidase (DPP) IV+ Fischer 344 rats were transplanted into the liver of DPPIV- mutant Fischer 344 rats after a combined treatment with retrorsine, a pyrrolizidine alkaloid that blocks the hepatocyte cell cycle, and two-thirds partial hepatectomy. In female rats, clusters of proliferated DPPIV+ hepatocytes containing 20 to 50 cells/cluster, mostly derived from single transplanted cells, were evident at 2 weeks, increasing in size to hundreds of cells per cluster at 1 month and 1000 to several thousand cells per cluster at 2 months, representing 40 to 60% of total hepatocyte mass. This level of hepatocyte replacement remained constant for up to 1 year, the duration of experiments conducted. In male rats, liver replacement occurred more rapidly and was more extensive, with transplanted hepatocytes representing 10 to 15% of hepatocyte mass at 2 weeks, 40 to 50% at 1 month, 90 to 95% at 2 months, 98% at 4 months, and 99% at 9 months. Transplanted hepatocytes were integrated into the parenchymal plates, exhibited unique hepatic biochemical functions, and fully reconstituted a normal hepatic lobular structure. The extensive proliferation of transplanted cells in this setting of persistent inhibition of resident hepatocytes represents a new general model to study basic aspects of liver repopulation with potential applications in chronic liver disease and ex vivo gene therapy.

Adenosine Triphosphatases↗

PubMed1997

Role of cholesterol synthesis and esterification in the growth of CEM and MOLT4 lymphoblastic cells.

CEM and MOLT4 are human T-cell lines isolated from patients with acute cell leukaemia. In culture they show important differences in cholesterol metabolism, CEM being less efficient at synthesizing cholesterol and having a lower activity of 3-hydroxy-3-methylglutaryl-CoA (HMGCoA) reductase. To investigate further the relationship between regulation of intracellular cholesterol metabolism at various steps and rate of cell growth, cholesterol synthesis, esterification and efflux were evaluated in CEM and MOLT4 cells at different times during exponential and stationary growth in vitro. It was shown that, although CEM cells have a lower rate of cholesterol synthesis, they grow at a faster rate than MOLT4 cells. However, CEM cells exhibit an increased capacity to esterify cholesterol associated with a decreased efflux of newly synthesized cholesterol into the medium. These results provide evidence for an association between the capability to synthesize and retain cell cholesterol esters and the growth rate potential.

Acetates↗

PubMed1997

Transient inhibition by orotic acid does not abolish the in vivo response of rat hepatocytes to a direct mitogen, lead nitrate.

BACKGROUND: Orotic acid (OA) is able to inhibit hepatocyte proliferation in vivo induced by 2/3 partial hepatectomy. The present studies were aimed at establishing: (i) whether OA also inhibits hepatocyte proliferation induced by a direct mitogen and, if so (ii) whether the stimulus provided by the mitogen is still expressed following transient inhibition by OA. METHODS/RESULTS: In the first experiment male Wistar rats were injected with either lead nitrate (100 mumol/kg, i.v.) or saline and 20 h later some animals receiving the mitogen were also implanted with a 400-mg OA tablet (as OA-methyl ester. i.p.). Multiple injections of 3H-thymidine were given to each rat (50 microCi each, 6 h apart, i.p.) until 2 h before killing. All groups were killed 3 days after the initial treatment. Results indicated that OA almost completely inhibited hepatocyte DNA synthesis and labelling induced by lead nitrate (e.g. labelling index was 1.9 +/- 0.5% in the saline-treated group, 44.7 +/- 4.0% in the lead nitrate group and 1.4 +/- 0.3% in the group receiving lead nitrate + OA). Based on the above results, in a second experiment rats were given a similar dose of lead nitrate and a subset of animals was implanted 20 h later with a 400-mg OA tablet, as previously described. Multiple doses of 3H-thymidine were again given to each rat (20 microCi each, 6 h apart) until 2 h before killing. Animals from both groups were killed at 3, 6 or 8 days after lead nitrate. Results indicated that, while at day 3 lead nitrate-induced DNA synthesis was effectively inhibited by OA, at day 6 the proliferative response was resumed in the group receiving OA. Cumulative labelling index over 6 days was 30.3 +/- 1.4 in rats given the mitogen alone and 52.1 +/- 2.2 in the group exposed to lead nitrate + OA. CONCLUSIONS: These data indicate that: (i) OA is also able to inhibit hepatocyte proliferation induced by a direct mitogen such as lead nitrate; this, in turn, suggests that its inhibitory effect is not unique to the stimulus elicited by partial hepatectomy. (ii) The proliferative response triggered by the mitogen is not abolished by the transient (3-4 days) inhibitory phase imposed by OA. Possible mechanisms underlying these effects are considered in the discussion.

Animals↗

PubMed1996

Epsilon PKC acts like a marker of progressive malignancy in rat liver, but fails to enhance tumorigenesis in rat hepatoma cells in culture.

We have analyzed the expression pattern of epsilon protein kinase C (PKC) in normal liver tissue, in hyperplastic liver nodules and in hepatocellular carcinomas generated in the rat with the Solt-Farber protocol. A progressive increase in PKC epsilon expression was observed in nodules and carcinomas compared to normal liver tissue, suggesting that the expression level of this PKC isoenzyme could be associated with increased malignancy. To test this hypothesis, the well differentiated, poorly tumorigenic MH1C1 rat hepatoma cell line was stably transfected with a full length epsilon PKC cDNA. No increase in growth rate, saturation density, soft agar growth or in vivo tumorigenicity was observed in transfected cells, compared to parental or mock-transfected cells. These results indicate that epsilon PKC does not seem to participate in signaling pathways involved in neoplastic transformation or malignant progression in our liver cell model. The fact that epsilon PKC overexpression is tumorigenic in several other cell types suggests that this effect might be strictly cell- and tissue-specific.

Animals↗

PubMed1996

A subnecrogenic dose of diethylnitrosamine is able to initiate hepatocarcinogenesis in the rat when coupled with fasting/refeeding.

Caloric restriction causes a generalized decrease in growth rate and has been repeatedly associated with an inhibitory effect on cancer development in several systems. In contrast, exposure to complete fasting followed by refeeding is a metabolic condition associated with increased cell turnover in different organs, including the liver. The present study examines whether such condition is able to sustain the induction of initiated hepatocytes following a subnecrogenic dose of diethylnitrosamine (DENA). Male Fisher-344 rats were fasted for 4 days and 1 day after refeeding they were given a single dose of DENA (20 or 200 mg/kg body wt, i.p.). Negative and positive control groups were fed ad libitum and injected with 20 and 200 mg/kg of DENA, respectively. One week later all animals were subjected to the resistant hepatocyte model for the selection of hepatocyte nodules and they were killed 2 weeks thereafter. Results indicated the presence of gamma-glutamyltransferase (GGT) positive foci and nodules (38 +/- 7/cm2) in rats regularly fed and given 200 mg/kg of DENA, while virtually no focal lesions (< 1/cm2) were found in the group receiving 20 mg/kg of DENA and fed throughout the experiment. However, a significant number of GGT positive foci/nodules (14 +/- 7) also developed in rats exposed to fasting and given 20 mg/kg of DENA 24 h after refeeding. No evidence of hepatocellular necrosis was found in the latter group following DENA administration. No effect of fasting was observed when rats received 200 mg/kg of DENA. It is concluded that fasting/refeeding provides conditions which are able to sustain initiation in rat liver by a subnecrogenic dose of a carcinogen. These findings are in contrast with the commonly reported inhibitory effect of chronic food restriction on various stages of carcinogenesis, including initiation.

Animals↗

PubMed1995

Protein kinase C isozymes during liver regeneration.

Protein kinase C isozyme (alpha, beta, delta and zeta) activities have been studied in compensatory cell proliferation at 20 and 24 hours after partial hepatectomy. Chromatographic analysis of PKC isozymes in male rats showed an activation of delta at 20 h after partial hepatectomy and of alpha, beta and zeta at 24 in correspondence with S phase peak. A peculiar sexual dimorphism, which matched sexual differences in DNA synthesis, has been observed. The administration of an excess of choline was able to modulate the protein kinase C isozyme pattern in females in relation to DNA synthesis and c-myc expression. Our data suggest that alpha, beta and zeta PKC positively regulated, while delta negatively controlled the liver compensatory growth after partial hepatectomy.

Animals↗

PubMed1995

Sexual dimorphism in the regulation of cell turnover during liver hyperplasia.

A sexual dimorphism occurs in liver cell proliferation following partial hepatectomy, female liver regenerating faster than male, while a continuous excess of choline to females shifts their growth pattern toward that of males (L. Tessitore, P. Pani and M.U. Dianzani, Carcinogenesis, 13 (1992) 1929). In this study we have investigated (a) if the same sexual modulation occurs in a different type of liver growth, hyperplasia induced by a direct mitogen and (b) if the pre-administration of choline to females is able to modulate this dimorphism. Liver hyperplasia induced by lead nitrate, a potent mitogen, has also shown a peculiar sexual dimorphism in all phases of the proliferative process. In contrast with liver regeneration after partial hepatectomy, the mitogenic action of lead nitrate was less effective and was delayed in females as compared with males, by evaluating liver weight, protein accumulation, DNA synthesis and mitotic index. These results were also confirmed by the trend of liver regression by apoptosis. The apoptotic index was higher in males than in females. A prolonged administration of an excess of choline has partially filled these sexual differences, since choline has moved, in females, all the observed parameters (liver weight, protein accumulation, DNA synthesis, mitotic and apoptotic indexes) to values closer to those observed in males.

Animals↗