Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cancer vulnerabilities”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed1985

Symposium on infections in the compromised host. Hematologic effects of cancer chemotherapy.

Use of the antineoplastic agents frequently causes myelosuppression and neutropenia. Neutropenic patients often fail to manifest the usual signs and symptoms of infection; they are unable to mount an adequate inflammatory response and infection disseminates rapidly. There is a direct correlation between the degree of granulocytopenia and the incidence and severity of infections. During the period of granulocytopenia (the vulnerable period) the risk of infection is high. While safeguarding the patient throughout the entire period of hospitalization, nurses should be more vigilant during this time. They must be alert to subtle signs of infection and the patient should be monitored closely for increased temperature (greater than or equal to 101 degrees F), mouth sores, sore throat, cough, congestion, or dysuria. The patient undergoing chemotherapy faces many threats to survival. This patient also offers an extraordinary challenge to nursing practitioners because good care may significantly improve the patient's quality and length of life.

Antineoplastic Agents↗
PubMed1994

Optimism versus pessimism predicts the quality of women's adjustment to early stage breast cancer.

BACKGROUND: Recent studies indicate that breast cancer patients do not usually experience the devastating psychological consequences once viewed as inevitable. However, some adjust to the disease more poorly than others. This study examined the personality trait of optimism versus pessimism as a predictor of adjustment over the first year, postsurgery. METHODS: Seventy women with early stage breast cancer reported on their general optimism-pessimism at diagnosis. One day before surgery, and at 3-month, 6-month, and 12-month follow-ups, they reported their subjective well-being (mood scales and a measure of satisfaction with life). At follow-ups, they also rated their sex lives, indicated how much physical discomfort was interfering with their daily activities, and reported on thought intrusion. RESULTS: Pessimism displayed poorer adjustment at each time point by all measures except interference from pain. Even controlling for previous well-being, pessimism predicted poorer subsequent well-being, suggesting that pessimism represents a vulnerability to a negative change in adjustment. In contrast, effects of pessimism on quality of sex life and thought intrusion were not incremental over time. Additional analyses indicated that effects of the optimism-pessimism measure were captured relatively well by a single item from the scale. CONCLUSIONS: A sense of pessimism about one's life enhances a woman's risk for adverse psychological reactions to the diagnosis of, and treatment for, breast cancer. This finding suggests the potential desirability of assessing this quality informally in patients, to serve as a warning sign regarding the patient's well-being during the period surrounding and following surgery.

Adaptation, Psychological↗
PubMed2002

Attachment and cancer: a conceptual integration.

Cancer traditionally has been explained by the biomedical model; however, it is limited in comprehensively accounting for all factors in this disease. Recently, it has been suggested that a broader theoretical framework that includes psychosocial components in cancer is needed to complement the traditional approach. The purpose of this article, therefore, is to explore the utility of attachment theory as a biopsychosocial model of both development and health. Attachment, a developmental theory, explains how repeated interactions between caregiver and child in the early years establish lifelong psychosocial, physiological, affective, and cognitive patterns as well as enduring patterns of stress response to threat or illness. Despite attachment theory's biopsychosocial foundation, the application of attachment security as a factor in physical health and psychosomatic medicine is relatively recent. The current work reviews attachment theory and psychosocial literature with regard to cancer and follows with a novel attempt to conceptually integrate both bodies of literature. A concluding integrative model of attachment theory and the type C behavior pattern is provided to illustrate potential links and integrative processes that may lead to disease resilience or vulnerability.

Adaptation, Psychological↗
PubMed2000

Hepatocellular carcinoma: an emerging problem with hepatitis C.

Hepatocellular carcinoma (HCC) is emerging as a major problem in the United States, primarily due to the development of liver cancer in patients with cirrhosis secondary to the hepatitis C virus. The diagnosis of HCC in patients with underlying cirrhosis can be achieved at an early stage if appropriate diagnostic measures are pursued by primary care physicians and gastroenterologists. African Americans are particularly vulnerable in developing HCC since their response to current therapy for chronic hepatitis C is less than optimal.

California↗
PubMed1996

[You have cancer. A qualitative study of women's immediate reactions to diagnosis of breast cancer].

92 women, 70 years and younger, consecutively admitted to Rogaland Central Hospital with a new diagnosis of breast cancer were interviewed the day before surgery. The aim of the study was to explore the women's reactions to the diagnosis. During the interview the patients were asked to speak for five minutes about what they felt, thought and did after learning they had cancer. The narratives were taped and analysed. The reactions are grouped under the headings: mental preparation, problem focusing, emotional and bodily reactions, coping strategies and support. There was a wide range of reactions, probably because of differences in coping ability, social support and vulnerability. The patients' need for thorough information is pointed out.

Adaptation, Psychological↗
PubMed2000

Epidemiology, stage at diagnosis, and tumor biology of breast carcinoma in multiracial and multiethnic populations.

All women, regardless of their racial or ethnic origin or heritage, are at risk of developing breast cancer. Variations in breast carcinoma incidence rates among multicultural populations suggest that etiologic factors differ in their biologic expression and impact on disease outcome. Key among those factors that affect breast carcinoma development are the roles of genetics and the environment, the reproductive experience and the effects of endogenous and exogenous hormones in women, the change in immune status and host vulnerability, and the biologic determinants of breast carcinoma. Cultural dynamics, sociodemographic differences, and behavioral characteristics across population subgroups modulate how biologic disease is expressed among different races and ethnic groups. These interactions contribute to the observed variations in breast carcinoma incidence, mortality, and survival. Stage, a measure of disease status, is used to assess prognosis, plan treatment, and evaluate outcome. Numerous studies have reported a more advanced stage of breast carcinoma at diagnosis in racial/ethnic subgroups, especially among women from African American, Hispanic, American Indian, and native Hawaiian cultures. Factors associated with advanced stage at diagnosis in multicultural populations range from changes in the basic biological characteristics at the molecular and cellular level, to more complex behavioral attributes unique to a particular multicultural population, to societal issues-such as access to care and socioeconomic conditions-all of which impact on the health measure called "stage at diagnosis." Rapid advancements in knowledge of cancer biology and of genetic markers and tumor products are providing new mechanisms for identifying etiologic pathways that can be utilized for better screening, detection, treatment and monitoring of disease. Further studies are needed that evaluate the biologic and molecular alterations in tumor development, progression, and response to therapy. Public health attention needs to be directed toward the societal influences that impact breast carcinoma development, as well as augmenting recognition of the need for culturally appropriate, broad-based behavioral changes at the community level. In addition, continued efforts are needed to ensure the inclusion of multicultural population subgroups and minority investigators in all aspects of research-basic, clinical and applied.

Adult↗
PubMedDate not supplied

Adrenal toxicity in dogs and cats as a contributing cause of hormonal and immune destabilization.

The adrenal cortex is regarded as the organ most vulnerable to toxicity within the endocrine system. The production of cortisol, among the many steroidal hormones produced by the cortex, may suffer as a result. In a veterinary clinical practice, household dogs and cats with a wide variety of diseases ranging from allergies to cancer commonly have a cortisol deficiency or defect that triggers endocrine imbalances and immune system destabilization. The causes of deficient cortisol are linked primarily to genetics but also to acquired adrenal damage likely stemming from environmental toxins. An innovative blood test to determine relevant endocrine-immune imbalances in pets and a treatment method based on low-dosage steroidal medication, as a form of cortisol replacement therapy, are described. Despite a prevailing reluctance to use steroidal medications long term because of the fear of side effects, extended and even life-time usage of these medications at low, physiologic dosages has been applied successfully for decades and appears to be gaining wider acceptance. The validity of a combined testing and treatment method for humans based on the veterinary model deserves investigation as a tool with which to identify and correct toxic damage to adrenal function.

Adrenal Cortex↗
PubMed2002

The role of high-dose chemotherapy in the treatment of non-small cell lung cancer.

The literature on high-dose chemotherapy in non-small cell lung cancer (NSCLC) with autologous bone marrow or peripheral blood stem cell transplantation does not - as of yet - provide evidence of relevant benefits. At the same time, the significant risks of treatment-related morbidity and mortality associated with dose-intensified chemotherapy in this vulnerable patient population are increasingly recognized. Whether the advent of new cytotoxic agents such as the Taxans or newer Topoisomerase inhibitors will help to improve the hitherto unsatisfying results of high-dose chemotherapy in NSCLC, remains to be determined. The few ongoing studies in the area strive to examine such newer drug-combinations in a multimodality treatment concept combining neo-adjuvant chemotherapy or chemoradiation with surgery and adjuvant thoracic radiation therapy.

Antineoplastic Agents↗
PubMed2000

Psychosocial morbidity in prostate cancer: II. A comparison of patients and partners.

OBJECTIVE: To assess psychometrically a new questionnaire for measuring the psychosocial morbidity in patients with prostate cancer and in their partners, and to compare the morbidity of patients and their partners. PATIENTS AND METHODS: A sequential sample of patients with any stage of prostate cancer and attending general urology outpatient clinics was identified. The questionnaire was administered to 135 patients and their partners in their homes. The Hospital Anxiety and Depression Scale (HADS) questionnaire was also administered to permit construct validation of the new measure. Test-retest reliability was calculated by re-administering the questionnaire to 60 individuals. The hypothetical general cancer distress and social subscales of the questionnaire were also tested for internal consistency. Psychosocial morbidity scores obtained by the patients and partners were compared. RESULTS: The questionnaire had good test-retest reliability and construct validity when tested against the HADS. The general cancer distress and social subscales were internally consistent. General cancer distress was highly prevalent and significantly more severe in partners than in patients. There was some degree of general cancer distress in 47% of patients and 76% of partners, whereas severe distress was detected in 11% and 30%, respectively. Social morbidity was limited and of equal severity between the groups. Treatment-related worries and concerns about pain and physical limitation were more common among partners than patients, whereas there was no difference for worries about urinary symptoms. Sexual concerns were the least prevalent and were more of a problem for patients than partners. CONCLUSION: Psychosocial morbidity in prostate cancer is highly prevalent, not only among patients but particularly among their partners. The new questionnaire showed adequate psychometric properties for use in identifying individuals with significant psychosocial morbidity. Applying the questionnaire should permit emotional and informational support to be targeted at the most vulnerable.

Aged↗
PubMed1994

Avoidant attachment as a risk factor for health.

A style of coping with stress is described which has been observed in cancer patients and in highly dependent, insecurely attached individuals. This coping style includes the suppression of negative emotions and avoidance of support seeking. It is suggested that this pattern of responses is potentially dysfunctional insofar as it tends to perpetuate distress and may increase vulnerability to a broad range of illnesses. These considerations provide the basis for a provisional conceptual model, which links avoidant attachment style to the regulation of negative affect and to symptoms of psychological and physical ill-health. This is tested on a sample of young adults under stress and predictions from the model are largely supported.

Adaptation, Psychological↗
PubMed2026

Comprehensive In Silico Analysis Identifies MSTO1 and LIG1 as Candidate Biomarkers With Diagnostic and Prognostic Relevance in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a major cause of cancer-related mortality worldwide. Its poor clinical outcomes are largely attributed to late-stage diagnosis and the limited accuracy of currently available diagnostic and prognostic biomarkers. Therefore, identifying novel molecular markers with improved sensitivity, specificity, and therapeutic relevance is essential for enhancing early detection and guiding personalized treatment strategies. AIMS: To identify and prioritize novel candidate HCC biomarkers with diagnostic and prognostic value and potential therapeutic vulnerability using integrated multi-omics, survival, functional dependency, and tumor microenvironment analyses. METHODS AND RESULTS: We examined the mRNA and protein expression levels of 8 DEGs in HCC tissues in the TCGA and CPTAC datasets using UALCAN, which showed that MSTO1 and LIG1 were overexpressed consistently in HCC relative to normal liver tissues. Moreover, elevated expression levels of these genes were significantly associated with higher tumor grade and advanced stage. Kaplan-Meier plotter survival data confirmed that increased expression of MSTO1 and LIG1 was associated with poorer overall survival. The DepMap CRISPR knockout data confirmed a functional dependency of both genes in HCC cell lines. CBioPortal analyses provided characterization of genomic alterations and enabled enrichment analysis of co-expressed genes, and the TCGA-UALCAN pan-cancer analyses supported the assessment of tissue specificity across tumor types. TIMER3 analyses linked candidate gene expression with immune cell infiltration patterns. Diagnostic performance by ROC analysis showed excellent discrimination for MSTO1 (AUC = 0.987) and good discrimination for LIG1 (AUC = 0.897). Multivariate Cox regression with Benjamini-Hochberg FDR correction across the eight genes supported MSTO1 as a candidate independent prognostic factor after adjustment for tumor stage, grade, etiology, age, and sex (HR = 1.29, p = 0.035), whilst LIG1 showed no independent prognostic value. Promoter methylation of MSTO1 and ADH4, assessed via UALCAN, showed that both genes were significantly differentially methylated in the promoter region of primary HCC tissues compared with normal liver tissues. Our study also confirmed the biological and clinical relevance of established HCC biomarkers: TERT, IRAK1, and ADH4. CONCLUSION: MSTO1 and LIG1 emerged as candidate diagnostic biomarkers in HCC. Additionally, MSTO1 showed a candidate prognostic association with overall survival that remained significant after adjusting for tumor stage, grade, and etiology, as well as patients' age, but not after further adjustment for AFP status. Functional data also highlighted MSTO1 as a candidate therapeutic dependency. On the other hand, LIG1 showed no independent prognostic association in either multivariate model. Their differential expression and functional essentiality in HCC cell lines highlighted their value for further experimental and independent-cohort validation before potential integration into biomarker development pipelines aimed at improving early detection and targeted therapy in HCC.

Humans↗
PubMedDate not supplied

Prognostic significance of keratinization in nasopharyngeal carcinoma.

INTRODUCTION: Keratinization may be a vulnerable aid in predicting response to therapy for nasopharyngeal carcinoma. METHODS: The presence or absence of keratin in biopsy specimens was correlated with tumor behavior, locoregional control, patterns of failure, and survival of patients irradiated for nasopharyngeal carcinoma. RESULTS: Patients with keratinizing squamous-cell cancers (World Health Organization [WHO] type 1) had a higher incidence (76%) of locally advanced tumors than those with nonkeratinizing (WHO type 2) and undifferentiated (WHO type 3) cancers (55%). The former group of patients had a lower incidence (29%) of lymph node metastases than the later group (70%). Primary tumor was controlled in 62% and neck nodes were controlled in 82% of all patients. Primary tumor control rates were 29% in patients with keratinizing squamous-cell cancers and 79% in those with nonkeratinizing and undifferentiated cancers (P = .001). Nodal control rates were 76% for keratinizing squamous-cell cancer and 85% for nonkeratinizing and undifferentiated cancers (P = .001). The incidence of distant metastases was 6% in patients with keratinizing squamous-cell cancer and 33% in those with nonkeratinizing and undifferentiated cancers (P = .001). Patients with keratinizing squamous-cell cancers, even though they had a lower incidence of lymphatic and distant metastases, had a poorer survival rate because of a higher incidence of deaths from uncontrolled primary tumors and nodal metastases. The 5-year survival rates were 35% for all patients, 6% for those with keratinizing squamous-cell cancers, and 51% for nonkeratinizing and undifferentiated cancers respectively (P = .001). CONCLUSION: Higher doses of external beam radiotherapy with or without brachytherapy boost may be needed to improve local control and survival of patients with keratinizing squamous-cell carcinoma of the nasopharynx, whereas an effective systemic therapy is needed for nonkeratinizing and undifferentiated cancers, which tend to metastasize.

Adult↗
PubMedDate not supplied

Practical applications of cutaneous colorimetry.

Dermatologists have long tried to quantify skin color and had few results until the advent of tristimulus colorimetry. With the Minolta colorimeter, quantification of skin color has become a simple matter: skin color can be measured rapidly, noninvasively, and reproducibly. The instrument, which can be used by paramedical staff, provides data that lend themselves for comparison, irrespective of where they are collected. The instrument has enabled definition of the range of physiologic values of skin color, and has revealed marked variations between exposed and nonexposed skin. Constitutional skin color characterizes an individual's phenotype better than facultative skin color and is highly indicative of vulnerability to sunlight. It is therefore a parameter for predicting the immediate and delayed response to light stimulation. On the practical level, colorimetric skin color values can be used to study pigmentation capacity, to program photochemotherapy, and to predict the risk of, and prevent, actinic cancer. Colorimetry can be used to quantify the intensity of erythema of spontaneous and experimental lesions. It has been used to monitor the efficacy of anti-inflammatory treatment of psoriasis and atopic dermatitis. It has also been used in the study of reactions induced by physical and allergic stimuli. Finally, colorimetry is useful in cosmetology for choosing appropriate sunscreens, for studying the effect of depigmentation products, and for determining the delicacy of detergents, and in any other situation that requires the measurement of parameters correlated with skin color that cannot be appreciated by visual observation.

Beauty Culture↗
PubMed2006

Coffee and health: a review of recent human research.

Coffee is a complex mixture of chemicals that provides significant amounts of chlorogenic acid and caffeine. Unfiltered coffee is a significant source of cafestol and kahweol, which are diterpenes that have been implicated in the cholesterol-raising effects of coffee. The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including type 2 diabetes mellitus, Parkinson's disease and liver disease (cirrhosis and hepatocellular carcinoma). Most prospective cohort studies have not found coffee consumption to be associated with significantly increased cardiovascular disease risk. However, coffee consumption is associated with increases in several cardiovascular disease risk factors, including blood pressure and plasma homocysteine. At present, there is little evidence that coffee consumption increases the risk of cancer. For adults consuming moderate amounts of coffee (3-4 cups/d providing 300-400 mg/d of caffeine), there is little evidence of health risks and some evidence of health benefits. However, some groups, including people with hypertension, children, adolescents, and the elderly, may be more vulnerable to the adverse effects of caffeine. In addition, currently available evidence suggests that it may be prudent for pregnant women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion or impaired fetal growth.

Adult↗
PubMed2026

Precision medicine and parental experience: a longitudinal study of psychosocial responses to germline genomic results in pediatric oncology.

INTRODUCTION: Precision medicine has become central to pediatric oncology, with germline genomic sequencing commonly integrated into routine care. Families must interpret complex genomic findings during emotionally vulnerable periods, generating mixed reactions ranging from clarity and relief to anxiety and uncertainty. Palliative care clinicians, genetic counselors, psychologists, social workers, and oncology providers may each contribute to supporting families as they interpret and integrate these findings over the course of a child's cancer care and beyond. Little is known about the trajectory of parental emotional and cognitive responses after receiving germline sequencing results, limiting clinicians' ability to anticipate support needs across the cancer care continuum. This study quantitatively examines parental emotional and cognitive responses across time following disclosure of germline sequencing results in a pediatric oncology setting. METHODS: Parents (n = 218) self-reported sequencing-related distress, positive feelings, intrusive thoughts, certainty, and self-efficacy using validated measures at two longitudinal follow-up points after disclosure of their child's germline test results. Outcomes were compared across germline test result types (pathogenic/likely pathogenic [P/LP], n = 31 [14%]; variants of uncertain significance [VUS], n = 86 [39%]; and negative, n = 101[46%]). RESULTS: Parents of children receiving P/LP or P/LP+VUS results reported significantly higher distress yet greater positive feelings than parents receiving negative results. Notably, certainty and self-efficacy increased from Timepoint 1 (median 254 days following return of results) to Timepoint 2 (median 537 days). Intrusive thoughts did not significantly differ by genetic result type or change over time; however, the factors contributing to intrusive thoughts could not be determined from the current study. DISCUSSION: These findings provide insight into how families adapt to germline genomic information following a pediatric cancer diagnosis. As precision medicine becomes increasingly embedded in pediatric oncology, structured follow-up and communication that address families' evolving informational and psychosocial needs are essential to ensure care that is scientifically precise, emotionally attuned, and centered on the family experience.

family-centered care↗
PubMed2003

Long-term coping of Holocaust survivors: a typology.

BACKGROUND: The nature of long-range impairment resulting from exposure to the atrocities of the Holocaust has been studied extensively. Some survivors reported a high level of psychological distress, while others, who were exposed to similar experiences, reported little, if any, symptoms. The present study aimed to validate Danieli's (1-3) typology of differentiated patterns of long-term coping and adaptation among Holocaust survivors in an Israeli sample. METHOD: A sample of 150 Holocaust survivors participated in this study. Data were gathered as part of a larger study that assessed long-term coping styles of elderly Holocaust survivors when confronted with another life-threatening event, namely cancer. RESULTS: The results point to the heterogeneous coping styles of Holocaust survivors and enable the formulation of a Survivor's Typology describing three types of adaptation: The "Victim," the "Fighter" and "Those Who Made It." The "Victim" type was found to be the most vulnerable. The "Fighter" and "Those Who Made It" types, who comprised over 80% of the sample, reported successful adaptation in the aftermath of the Holocaust.

Adaptation, Psychological↗
PubMed2001

Synergistic effects of nicotine on arecoline-induced cytotoxicity in human buccal mucosal fibroblasts.

Areca quid chewing has been linked to oral submucous fibrosis and oral cancer. Arecoline, a major areca nut alkaloid, is considered to be the most important etiologic factor in the areca nut. In order to elucidate the pathobiological effects of arecoline, cytotoxicity assays, cellular glutathione S-transferase (GST) activity and lipid peroxidation assay were employed to investigate cultured human buccal mucosal fibroblasts. To date, there is a large proportion of areca quid chewers who are also smokers. Furthermore, nicotine, the major product of cigarette smoking, was added to test how it modulated the cytotoxicity of arecoline. At a concentration higher than 50 microg/ml, arecoline was shown to be cytotoxic to human buccal fibroblasts in a dose-dependent manner by the alamar blue dye colorimetric assay (P<0.05). In addition, arecoline significantly decreased GST activity in a dose-dependent manner (P<0.05). At concentrations of 100 microg/ml and 400 microg/ml, arecoline reduced GST activity about 21% and 46%, respectively, during a 24 h incubation period. However, arecoline at any test dose did not increase lipid peroxidation in the present human buccal fibroblast test system. The addition of extracellular nicotine acted synergistically on the arecoline-induced cytotoxicity. Arecoline at a concentration of 50 microg/ml caused about 30% of cell death over the 24 h incubation period. However, 2.5 mM nicotine enhanced the cytotoxic response and caused about 50% of cell death on 50 microg/ml arecoline-induced cytotoxicity. Taken together, arecoline may render human buccal mucosal fibroblasts more vulnerable to other reactive agents in cigarettes via GST reduction. The compounds of tobacco products may act synergistically in the pathogenesis of oral mucosal lesions in areca quid chewers. The data presented here may partly explain why patients who combined the habits of areca quid chewing and cigarette smoking are at greater risk of contracting oral cancer.

Analysis of Variance↗
PubMed1991

Role of persistent, non-genotoxic tissue damage in rodent cancer and relevance to humans.

This review has focused on the importance of cellular proliferation in neoplasia induced by nongenotoxic carcinogens and has not attempted to address the mechanisms involved in the progression from the hyperplastic to the neoplastic state. Major advances in this area are likely in the next decade and should explain how cells in an abnormally high proliferative state are rendered more vulnerable either to the action of endogenous or environmental mutagens or to defects in cell reproduction, thus providing the stimulus for progression to neoplasia (165). In this review evidence has been presented to support the hypothesis that sustained tissue damage induced by nongenotoxic compounds in rodents predisposes to tumor development. The evidence has been obtained by drawing from the published findings of experimental rodent studies conducted over the past 50 years. The experience gained at various sites in the rodent including the connective tissue, liver, bladder, and forestomach shows the existence of a threshold dose for various test materials/agents, below which neither sustained tissue damage nor tumor induction occurs but above which level both effects are manifest. Taken collectively, an overall picture emerges that sustained cell proliferation renders various sites in the rodent vulnerable to tumor development. The validity of this hypothesis is of importance to the evaluation of carcinogenic risk of chemicals to humans. For those nongenotoxic carcinogens known to cause characteristically defined and sustainable tissue damage as a precursor of tumor development in rodents, it should be possible to establish a threshold dose below which both effects disappear and upon which a safety margin in humans can be based. Some limited evidence supports an association between chronic tissue injury and neoplastic development in humans. Note, however, that certain types of induced tissue damage may be rodent-specific and therefore have no relevance for humans. We conclude that the appearance of persistent tissue damage predisposes to tumor development in rodents exposed to nongenotoxic carcinogens and that systematic studies in rodents should provide a rational basis for arriving at a safety margin in humans exposed to such agents.

Animals↗