Median Period Of Survival Research Articles

Effect of Flavonoid-Rich Foods and Flavonoids on the Risk of Cancer Recurrence Among Korean Breast Cancer Survivor

Abstract Objectives Flavonoid intakes have been shown to associate with breast cancer incidence, but it is not clear the association between flavonoids and cancer recurrence. The purpose of the present study was to investigate the hypothesis that intakes of flavonoids and flavonoid-rich foods were negatively associated with cancer recurrence. Methods Among 572 women after breast cancer surgery, 66 patients had cancer recurrence during follow–up until 114 months with a median period of disease-free survival of 43 months ranged 6–103 months. Dietary data were collected using structured 24-h dietary recall, and the intake of flavonoid was calculated based on the Korea Rural Development Administration flavonoid database. Results There was no significant association of flavonoid and flavonoid-rich food intake with cancer recurrence and disease-free survival among all patients. On the other hand, among overweight and obese patients, Kaplan-Meier survival curves revealed a significant effect of dietary flavonoids (P = 0.04) and flavonoid-rich foods (P = 0.03) on disease-free survival, but not overall survival. Intakes of flavonoid (HR = 0.244, 95% CI: 0.09–0.66) and flavonoid-rich food (HR = 0.223, 95% CI: 0.08–0.59) were also negatively associated with cancer recurrence after adjusting for confounding factors in overweight and obese patients. Consumption of flavonoids and flavonoid-rich foods was lower in overweight and obese patients with cancer recurrence than those without recurrence. Conclusions To the best of our knowledge, this was the first study to examine the association between flavonoid intake and cancer recurrence/disease-free survival in breast cancer patients. The present study suggested that intakes of flavonoids and flavonoid-rich foods could have a beneficial effect on cancer recurrence among overweight and obese breast cancer survivors. Further clinical studies are needs to confirm whether supplementation of flavonoids reduces cancer recurrence. Funding Sources This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1A2B6002486).

Oral Presentation

Oral Presentation

Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks.

Objectives:The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure for these rare diseases.Methods:Based on incident pericardial and tunica vaginalis testis mesothelioma cases collected from the Italian national mesothelioma registry (ReNaM) in the period 1993–2015, incidence rates, survival median period and prognostic factors have been evaluated. A case–control study has been performed to analyze the association with asbestos exposure (occupational and non-occupational) for these diseases.Results:Between 1993 and 2015, 58 pericardial (20 women and 38 men) and 80 tunica vaginalis testis mesothelioma cases have been registered with a mean annual standardized (world standard population as reference) incidence rates of 0.049 (per million) in men and 0.023 in women for the pericardial site, and 0.095 for tunica vaginalis testis mesothelioma. Occupational exposure to asbestos was significantly associated with the risk of the diseases [odds ratio (OR) 3.68, 95% confidence interval (CI) 1.85–7.31 and OR 3.42, 95% CI 1.93–6.04 in pericardial and tunica vaginalis testis mesothelioma, respectively]. The median survival was 2.5 months for pericardial and 33.0 months for tunica vaginalis testis mesotheliomas. Age was the main predictive factor for survival for both anatomical sites.Conclusions:For the first time in an analytical study, asbestos exposure was associated with pericardial and tunica vaginalis testis mesothelioma risk, supporting the causal role of asbestos for all anatomical sites. The extreme rarity of the diseases, the poor survival and the prognostic role of age have been confirmed based on population and nationwide mesothelioma registry data.

Abstract S4-07: Tamoxifen resistance driven by the DNA cytosine deaminase APOBEC3B in recurrent estrogen receptor positive breast cancer

Abstract Recent studies have implicated the DNA cytosine deaminase APOBEC3B as a major source of mutation in breast cancer. APOBEC3B explains a large proportion of both dispersed and clustered cytosine mutations, the latter of which are also called kataegis. APOBEC3B expression levels correlate with poor outcomes for patients with estrogen receptor positive breast cancer. While targeted therapies, such as tamoxifen, are available to treat these tumors, secondary drug resistance often develops. Here we suppressed endogenous APOBEC3B in the estrogen receptor positive breast cell line MCF-7L with shRNA. Lowered levels of APOBEC3B did not affect in vitro growth or sensitivity to estradiol. In a xenograft model of tamoxifen therapy, suppression of APOBEC3B associated with prolonged responses to tamoxifen (p<0.05). Furthermore, APOBEC3B over-expression did not affect in vitro cell growth but accelerated the development of tamoxifen-resistant tumors in vivo. In addition, we studied two separate cohorts of 285 breast cancer patients who received first line treatment with tamoxifen for recurrent disease. High APOBEC3B expression levels measured in the primary tumor associated significantly with unfavorable progression free survival in multivariate analysis that included the traditional predictive factors (age, dominant relapse site, disease-free interval, estrogen receptor and progesterone receptor, and adjuvant chemotherapy; HR=1.67, p=0.0001). The median period of progression free survival was 7.5 months for patients with APOBEC3B high primary tumors and 13.3 months for those with APOBEC3B low tumors (p<0.0.0001). These studies demonstrate that APOBEC3B drives resistance to endocrine treatment with tamoxifen in recurrent disease. Citation Format: Harris R, Law E, Sieuwerts A, LaPara K, Leonard B, Starrett G, Temiz NA, Sweep F, Span P, Foekens J, Martens J, Yee D. Tamoxifen resistance driven by the DNA cytosine deaminase APOBEC3B in recurrent estrogen receptor positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S4-07.

Pemphigus vulgaris: a clinical study of 44 cases over a 20-year period.

Pemphigus vulgaris (PV) is a rare, life-threatening, autoimmune bullous disease with unpredictable progression and prognosis. This study aimed to analyze long-term outcomes in patients with PV, focusing on factors that may influence the prognosis of the disease, including the phenotype of PV, age at onset, multiplicity of mucosal involvement, relapse and remission rates, and survival functions. A retrospective analysis was conducted in 44 patients who were diagnosed and monitored from 1993 to 2012. Statistical analyses were conducted using the Mann-Whitney test and Kruskal-Wallis test. Survival data were analyzed using Kaplan-Meier and log rank tests. Fisher's exact test was used to assess statistical significance at P < 0.05. A total of 79.5% of patients were identified as having mucocutaneous PV. The female : male gender ratio was 1.58; in severe PV, this increased to 2.8. The difference between the genders in age at onset was statistically significant (P = 0.05). Furthermore, multiple mucosal involvements in the oral cavity and at other sites were associated with severe mucocutaneous PV. Multiple relapses occurred more frequently in patients with severe PV than in those with mild PV (P = 0.001). The remission survival of females was longer than that of males (P = 0.003). Poor prognosis factors include the severe mucocutaneous type of PV, especially in female patients, and multiple mucosal involvements in the oral cavity and other mucosal sites. Female patients were younger than male patients and were more often observed to have severe mucocutaneous PV and to have a higher median period of remission survival than male patients.

Modified FLOX as first-line chemotherapy for metastatic colorectal cancer patients in the public health system in Brazil: Effectiveness and cost-utility analysis

Incorporation of new drugs for treatment of metastatic colorectal cancer (mCRC) has led to a clear improvement in overall patient survival, the added cost of treatment, however, is a major concern worldwide. The cost-effectiveness of using a modified FLOX (mFLOX) regimen for treating mCRC patients was delineated. In this study, 82 consecutive mCRC patients were treated with leucovorin (LV) at 20 mg/m2 in combination with weekly bolus of 5-fluorouracil (5-FU) (500 mg/m2) for 6 consecutive weeks and oxaliplatin (85 mg/m2) at weeks 1, 3 and 5, every 8 weeks. Overall survival (OS) and toxicity were evaluated. A Markov Model with a 2-year time horizon and 2-week cycles was developed, comparing mFLOX and mFOLFOX6 in a Brazilian environment. Health outcomes were measured in quality-ajusted life years (QALYs). The median overall period of survival was 19 months, while the estimated 1-year survival was 75%. Response by RECIST was assessed in 33 patients. Partial response was observed in 39.4% of patients, while 36.3% were stable. The mFLOX regimen cost was BRL 9,000, while the mFOLFOX6 BRL 22,000 (1 EUR=2.29 BRL), leading to an incremental costed of BRL 13,000, considering a 20-week period of first-line therapy. The incremental effect of the mFOLFOX was of 0,117 QALY. The incremental cost-effectiveness ratio of mFOLFOX6 was of BRL 110,344/QALY. The sensitivity analysis detected no differences in the outcome measures. In conclusion, the mFLOX is an active regimen in mCRC patients, possibly providing a cost-effective option in public health systems.

Contribution of C-reactive protein to predicting overall survival in patients with advanced urothelial carcinoma: Development of a nomogram and evaluation by decision curve analysis.

280 Background: To accurately estimate the individual survival of patients with advanced urothelial carcinoma (UC), the application of prediction models such as nomograms has been warranted in clinical use. We therefore constructed a nomogram which included C-reactive protein (CRP) as a novel biomarker in order to increase its predictive accuracy. Furthermore, the clinical usefulness of this nomogram was evaluated by decision curve analysis which incorporated the negative consequences of each decision to generate a net benefit (Vickers et al, BMC Med Inform Decis Mak, 2008). Methods: A total of 232 consecutive patients with locally advanced or metastatic urothelial carcinoma (UC) were treated at our institute. Among them, 9 patients with missing data were excluded. The current study cohort was comprised of the remaining 223 patients. A nomogram predicting 6- and 12-month survival probability was developed based on the results of the final multivariate analytic model. To evaluate the efficacy of this nomogram, a quantified concordance-index (c-index) was computed and a decision curve analysis was performed. Results: Overall, 184 patients died of the primary disease and the remaining 39 were censored. The median follow-up period and length of overall survival were 5 and 6 months, respectively. The 6- and 12-month survival rates were 48% and 30% respectively. A nomogram was developed which included the parameters of age, PS, visceral metastasis, hemoglobin and CRP. The c-index of this prediction model was 0.79 compared with 0.75 for that of a model without CRP. The decision curve analysis revealed that a novel nomogram which incorporated CRP had a superior net benefit to that without CRP for most of the examined threshold probabilities. Conclusions: Incorporation of CRP increased the predictive accuracy of a prognostic nomogram for advanced UC. In clinical practice, this nomogram would contribute to the decision making process in the treatment of patients suffering from this form of carcinoma.

Clinical significance of pathological response in the breast cancer after neoadjuvant chemotherapy

OBJECTIVE Discuss the influential factor of pathologic response of tumor, axillary lymph nodes and extranodal soft tissue extension (ETE) in breast cancer after neoadjuvant chemotherapy and patients survival. 196 patients with II B to approximately III B stage breast cancer, all female, aged 47 (26-65), were treated by neoadjuvant chemotherapy, including intravenous injection of docetaxel and epirubicin for 21 days, followed by surgery. Then follow-up was conducted for 61 months (4-70 months). The influential factor of pathological response and relation between pathologic response and survival were analyzed. The follow-up rate of the 196 patients was 100%. 20 patients (10.2%) achieved pathological complete response (pCR), 108 patients (55.1%) achieved pathological part response (pPR), and 68 patients (34.7%) achieved pathological stable disease pSD. There was no correlation between pCR and clinical staging, and age of patients (both P > 0.05). But there was a correlation between pCR and the size of tumor, estrogen receptor (ER), progesterone receptor (PR), and pathological type (all P < 0.01). 27.0% of the metastatic axillary lymph-nodes showed down-staging. The overall 5-year survival rate was 62.8% (P < 0.01). The median period of survival was 61 month (P < 0.01). pCR is correlated with the size of tumor, ER, PR, and pathological type. Down-staging of primary tumor and metastatic axillary lymph-node are important prognosis factors.

What is the Price of survival in Hodgkin's lymphoma? Long‐term follow‐up of cured patients

The paper investigates the late complications of cured Hodgkin's lymphoma (HL) patients. Ninety cured HL patients between 1975 and 1994 were examined. The mean ages of patients at the time of diagnosing HL, and the median period of survival after diagnosis were 32 (11-70) years and 18 (10-30) years, respectively. Among the 90 patients, 73 are still alive, there is no information about 9 and 8 patients died, second malignant disease being the cause of death in 4 of them. Relapse was observed in 24 patients, of which 19 recovered after relapse and were included in the study then. Five patients had late relapse. In 38% of patients, cardiovascular changes, while in 32% pulmonary and pleural damages were observed. Disorders of the thyroid gland, overwhelmingly hypothyroidism, were found in 24%. Less frequently, a second malignant tumour (9%), damage to the skin, musculature, bones and genitourinary system (6%) as well as the gastrointestinal system could be detected. Treatment based on modern therapeutic approaches is expected to decrease the incidence of complications. Still the aim is early detection through close patient follow-up, which may improve the quality of life and decrease mortality as a result.

Epidemiological profile of cancer for Grand Bahama residents: 1988 - 2002

This retrospective and observational study is based on a review of data from the pathology ledgers and clinical records of the Rand Memorial Hospital, of diagnoses and deaths from cancer from 1988 to 2002 (15 years). The aim was to determine the cancer incidence, mortality, survival rates and the trends for the island of Grand Bahama, Bahamas. The records indicated at least 545 (males: 187; females: 358) new cancer diagnoses giving an approximate age-standardized annual incidence rate of 167.7 per 100,000. The most frequent cancers were, in males (except for skin keratinocytic cancers) prostate 21.9%, colon/rectum 12.8% and lung 6.4%; and in females: breast 45.3%, cervix uteri 16.8% and colon/rectum 6.4%. Of these cancers, 443 (81.3%) were diagnosed in the pathology department of the hospital with the median age at diagnosis of all persons being 52 years. This comprised 119 males and 324 females. Whereas the majority of breast and cervical cancers were histologically diagnosed locally, those of prostate and lung were not. During the period, 359 (males: 181; females: 178) persons had died from cancer; an annual age-standardized mortality rate of 114.8 per 100,000, with breast 19.2%, prostate 14.5% and colon/rectum 9.5% being the most frequent. The overall median period of survival was one year (range 0-14 years). The median survival for persons with cervix uteri was five years; for breast cancer, three years; colorectal cancer, 2 years; prostate, one year; and less than a year for lung cancer. The data on cancer were not easily obtained and this may be improved if a cancer registry is established on this second most populated island of The Bahamas.

Brain Metastasis after a Gastrectomy for Gastric Cancer

Purpose: The common features of brain metastases from gastric cancer are unknown because brain metastasis is an uncommon pattern of metastasis. The purpose of this study was to investigate the clinical features of and the prognosis for patients with brain metastases after a curative resection for gastric cancer. Materials and Methods: Twenty-one (21) cases of patients with brain metastases of gastric cancer, who had been treated at the Department of Surgery, Yonsei University College of Medicine, were assessed retrospectively. Results: The mean age was years (range: years), and the male-to-female ratio was 2.5 : .1. The most common neurologic symptom was headache (), and no patient was free from the neurologic symptoms. The incidence of parenchymal metastasis (PM: ) was higher than that of leptomeningeal metastasis (LM: ). Patients with gastric cancer and brain metastasis showed high rates of blood and lymphatic vessel invasion (lymphatic vessel invasion: ; blood vessel invasion: ). According to Lauren's classification, the incidence of intestinal types was 14/21 (), that of diffuse types was 3/21 () and that of mixed types was 4/21 (). The mean interval between the gastrectomy and the diagnosis of brain metastasis was months (PM: 26.8 months; LM: 20.3 months). The median period of survival after diagnosis of brain metastasis was 2 months for paren chymal metastasis and 0 months for leptomeningeal metastasis. Conclusion:.. During a follow-up period, patients with neurologic symptoms should be suspected of having brain metastasis. Early diagnosis and treatment is the only hope to prolong survival in such patients.

Leuprorelin Three-Month Depot in the Treatment of Advanced and Metastatic Prostate Cancer: Long-Term Follow-Up Results

Objectives: To determine median survival time, median time to tumor progression and maintenance of testosterone suppression (i.e. ≤50 ng/dl) during long-term treatment with subcutaneous injections of leuprorelin acetate 3-month depot (LAD-3M). In Germany 62 patients with advanced prostate cancer participated in a prospective, randomized, multicenter phase II trial as part of a European study. Of these, 37 patients entered the follow-up study. Methods: Standard clinical investigations and methods were employed in the study. Results: Twenty-five of the 62 (40.3%) patients died during the course of the study. No death had a causal relationship with the study drug. Median survival time, median time to tumor progression and median period of progression-free survival were 1,149 (3.1 years), 1,015 (2.8 years) and 680 days (1.9 years), respectively. Adequate suppression of testosterone serum levels to the castration range was confirmed. Objective and subjective response as well as the safety profile were comparable to previously published results with LAD-3M, LAD-1M and other LHRH analogues. Conclusions: The results of this follow-up study confirm long-term efficacy and safety of LAD-3M for treatment in advanced prostate cancer. LAD-3M is a suitable alternative to the established shorter-acting LHRH-a depot formulations.

Cadmium toxicity to rainbow trout Oncorhynchus mykiss walbaum and brown trout Salmo trutta L. over extended exposure periods

The toxicity of cadmium in water is well known, but there have been few reports on the long-term effects of this metal on fish at concentrations near the European inland water standard of 5 μg Cd liter −1. This paper describes experiments in which adult rainbow trout Oncorhynchus mykiss and brown trout Salmo trutta were exposed to cadmium concentrations near water quality standard levels for periods of up to 90 weeks. The survival and growth of these fish were assessed, and sperm and eggs were stripped from them to conduct early-life-stage tests. Continuous exposure of rainbow trout adults to cadmium concentrations of up to 5.5 μg Cd liter −1 did not affect their survival or growth. However, eggs obtained from rainbow trout exposed to 1.8 and 3.4 μg Cd liter −1 failed to develop to the fry stage. Oogenesis appeared to be delayed in brown trout exposed to 9.3 and 29.1 μg Cd liter −1, but the eggs and fry that were produced developed normally after fertilization. Adult brown trout suffered considerable mortality in the 29.1 μg Cd liter −1 treatment, with a median period of survival of 54 weeks.

Tuberculosis and HIV infection association in a rural district of northern Uganda: epidemiological and clinical considerations

59 (18.3%) of 323 patients with tuberculosis (TB) tested for HIV-1 antibody by ELISA technique (Wellcozyme) were seropositive. In the control group selected among the health personnel working in the Arua Hospital, 7.7% were found positive for HIV-1 antibody, thus showing a significantly lower prevalence compared with the TB patients (P < 0.005). The prevalence of HIV infection was 50% in the urban TB patients, 7% in TB patients living in rural areas surrounding Arua town and 1.6% in the peripheral rural setting. Of 27 TB patients with clinical AIDS, 18 died during the course of the study. The AIDS patients' survival rate was 46.4% 6 months after diagnosis, and 21.4% after 16 months, the median period of survival being 5.0 months. Risk factors, sputum conversion rate, clinical and radiological findings were analysed. No significant difference was found between seropositive and seronegative TB patients for clinical drug-related toxicity (P >; 0.05).

The benefit of cisplatin-based polychemotherapy for adenocarcinoma of the lung

We studied the efficacy of cisplatin-based polychemotherapy for adenocarcinoma of the lung. A total of 136 patients were randomized for treatment with either cyclophosphamide, Adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT). Radiation was given to the chests of patients at stage III. The differences in the response rate (35% in the CAPM arm and 13% in the MCT arm) were statistically significant (P less than 0.01). However, the significant difference was observed in stage-IV patients (CAPM, 33%; MCT, 4%; P less than 0.001) and not in stage-III patients (CAPM, 40%; MCT, 40%). The median period of survival was 9.5 months for the CAPM arm and 5.5 months for the MCT arm (P less than 0.035, Wilcoxon-Gehan test; P less than 0.1, log-rank test). Improved median survival for the CAPM regimen was demonstrated only by stage-IV patients (CAPM, 10 months; MCT, 5.5 months; P less than 0.025, Wilcoxon-Gehan test; P less than 0.05, log-rank test). The duration of the response, including PRs and NCs, was significantly different depending on the treatment, showing 5 months for the CAPM arm and 3 months for the MCT arm (P less than 0.05). The significant difference was also only observed in stage-IV patients. Myelosuppression was more severe with CAPM than with the MCT regimen. Nausea and vomiting were significantly increased in patients receiving the CAPM regimen. However, all toxicities were acceptable and there were no treatment-related deaths. We concluded that cisplatin-based chemotherapy, CAPM therapy, was of more benefit to patients with adenocarcinoma of the lung than MCT therapy.

The impact of Cd and different pH on the amphipod Gammarus fossarum koch (Crustacea: Amphipoda)

1. Acute toxicity tests were carried out at different pH-conditions (pH 4.5, 6.0 and 8.5) on the amphipod Gammarus fossarum Koch. 2. The median period of survival decreased with increasing pH in the presence of Cd. 3. Median lethal concentrations (24, 48 and 96 hr LC 50's) indicate that G. fossarum is highly sensitive to Cd at pH 8.5 (96 hr LC 50 proved to be 6.2 μg/l).

The susceptibility of Rattus rattus and Bandicota bengalensis to a new anticoagulant rodenticide, flocoumafen

The anticoagulant rodenticide flocoumafen was evaluated against Rattus rattus and Bandicota bengalensis. In no-choice 24 h feeding tests 100% mortality occurred at 0.00125% concentration of the poison in the bait in the case of B. bengalensis and at 0.00375% in R. rattus. Feeding of 0.0025% poison bait in 1-day, no-choice and 2-day choice tests resulted in 60% and 75% mortality of R. rattus, respectively, and 100% of B. bengalensis. The differences between the consumption of plain food in the pretreatment period and of poison bait in no-choice tests were non-significant, except in one case. The rodents consumed significantly more (P less than 0.01) poison bait than the plain alternative in the choice trials. Median period of survival and its 95% confidence limits of R. rattus and B. bengalensis, at the 100% mortality dose levels of the poison, were 6.3 (5.04-7.88) and 6.2 (4.92-7.81) days respectively.

Evaluation of coumatetralyl against two predominant murid species.

Coumatetralyl was evaluated in the laboratory against Bandicota bengalensis and Rattus rattus. Feeding tests with 0.0375% coumatetralyl baits produced 100% mortality after a single day feeding period in B. bengalensis and after a 10-day period in R. rattus. The anticoagulant bait is less palatable in comparison to plain bait. In the case of R. rattus, LFP50 and LFP98 and their 95% confidence limits were 3.89 (2.62-5.77) days and 11.22 (6.1-20.65) days respectively. Median period of survival and its 95% confidence limits of B. bengalensis and R. rattus were 4.7 (3.85-5.7) days and 11.2 (9.33-13.44) days respectively.

Heavy metal tolerance and metallothionein induction in fathead minnows: Results from field and laboratory investigations

AbstractToxicity studies were performed on two natural populations of fathead minnows (Pimephales promelas). One group of organisms was taken from a metal‐contaminated flyash pond associated with a coal‐fired power plant and the other population was collected from Newtown hatchery ponds. As determined in acute toxicity tests, ash pond minnows were significantly more tolerant of cadmium and copper than were hatchery minnows. At an exposure concentration of 6.0 mg Cd/L in moderately hard water, the median period of survival (LT50) for flyash pond minnows was 50.0 h, compared with 6.8 h for hatchery minnows. The LT50 values for ash pond and Newtown animals exposed to 0.50 mg Cu/L in moderately hard water were 17.0 and 4.5 h, respectively. Both populations were about equally tolerant of zinc. After ash pond minnows were transferred to reconstituted water in the laboratory, tolerance to cadmium and copper decreased significantly after 7 d. Conversely, tolerance was increased in hatchery minnows following acclimation in the laboratory to sublethal concentrations of cadmium. For example, after exposing hatchery minnows for 35 d to 10 μg Cd/L, an acute toxicity test gave LC50 values of 2.88 and 1.71 mg Cd/L for acclimated and control organisms, respectively. This induced tolerance in cadmium‐acclimated hatchery minnows was lost when organisms were transferred to cadmium‐free water for 7 d. The results justify the conclusion that fathead minnows develop increased tolerance to cadmium and copper following prolonged sublethal exposure to these metals, and that this metal‐induced tolerance is not sustained once organisms are removed from toxicant stress. As determined in biochemical studies, gill metallothionein concentrations followed the fluctuations in tolerance exhibited during cadmium acclimation and deacclimation. Thus, tolerance induction was, in part, attributed to increased production of metallothionein, a protein which selectively binds and deactivates cadmium, copper and certain other metals.

HEAVY METAL TOLERANCE AND METALLOTHIONEIN INDUCTION IN FATHEAD MINNOWS: RESULTS FROM FIELD AND LABORATORY INVESTIGATIONS

Toxicity studies were performed on two natural populations of fathead minnows (Pimephales promelas). One group of organisms was taken from a metal-contaminated flyash pond associated with a coal-fired power plant and the other population was collected from Newtown hatchery ponds. As determined in acute toxicity tests, ash pond minnows were significantly more tolerant of cadmium and copper than were hatchery minnows. At an exposure concentration of 6.0 mg Cd/L in moderately hard water, the median period of survival (LT50) for flyash pond minnows was 50.0 h, compared with 6.8 h for hatchery minnows. The LT50 values for ash pond and Newtown animals exposed to 0.50 mg Cu/L in moderately hard water were 17.0 and 4.5 h, respectively. Both populations were about equally tolerant of zinc. After ash pond minnows were transferred to reconstituted water in the laboratory, tolerance to cadmium and copper decreased significantly after 7 d. Conversely, tolerance was increased in hatchery minnows following acclimation in the laboratory to sublethal concentrations of cadmium. For example, after exposing hatchery minnows for 35 d to 10 μg Cd/L, an acute toxicity test gave LC50 values of 2.88 and 1.71 mg Cd/L for acclimated and control organisms, respectively. This induced tolerance in cadmium-acclimated hatchery minnows was lost when organisms were transferred to cadmium-free water for 7 d. The results justify the conclusion that fathead minnows develop increased tolerance to cadmium and copper following prolonged sublethal exposure to these metals, and that this metal-induced tolerance is not sustained once organisms are removed from toxicant stress. As determined in biochemical studies, gill metallothionein concentrations followed the fluctuations in tolerance exhibited during cadmium acclimation and deacclimation. Thus, tolerance induction was, in part, attributed to increased production of metallothionein, a protein which selectively binds and deactivates cadmium, copper and certain other metals.