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Biomedical subjects

J Russo

Publications and source records attributed to J Russo.

At least 109 records · Page 6Linked to original sources
PubMed1996

Weight changes in caregivers of Alzheimer's care recipients: psychobehavioral predictors.

Relationships of changes in body mass index (BMI) were examined with changes in psychobehavioral variables in spouse caregivers of individuals with Alzheimer's disease (n = 81) and matched spouses of controls (n = 86). Men caregivers had significantly greater BMI and obesity than men controls at both times. Over 15-18 months, women caregivers gained significantly more weight than did women controls. A trend for greater obesity occurred in women caregivers than in women controls at follow-up. Although weight gain was not related to psychobehavioral variables in controls, in men caregivers decreased perceived control and increased fat intake explained significant variance in weight gain. In women caregivers, increased anger control and increased calories explained weight gain. Such caregivers may be at risk for health problems.

Adult↗
PubMed1996

Variations in plasma lipid concentration during examination stress.

The effect of psychological stress on plasma lipids was studied in 40 law students (20 men and 20 women). Plasma cholesterol, triglyceride, and apolipoprotein concentrations were examined at the beginning of the quarter and during the week before final examinations. Cortisol, blood pressure, and heart rate, and self-reports of stress and workload were also measured to verify that examinations were associated with increased stress levels. Perceived stress, perceived workload, and cortisol increased before examinations. Low density lipoprotein cholesterol (LDL-C) increased 5.8 +/- 13.9 mg/dL, and apolipoprotein B (apo B) increased 2.9 +/- 4.0 mg/dL. High density lipoprotein cholesterol decreased in women only. These changes were not due to changes in dietary intake or indexes of plasma volume. However, changes in cortisol and changes in LDL-C and apo B were associated, suggesting a neuroendocrine component to the effects. These results suggest that episodic, stressful situations may lead to potentially atherogenic changes in lipid and lipoprotein concentrations.

Journal Article↗
PubMed1996

Mammary gland neoplasia in long-term rodent studies.

Breast cancer, the most frequent spontaneous malignancy diagnosed in women in the western world, is continuously increasing in incidence in industrialized nations. Although breast cancer develops in women as the result of a combination of external and endogenous factors such as exposure to ionizing radiation, diet, socioeconomic status, and endocrinologic, familial, or genetic factors, no specific etiologic agent(s) or the mechanisms responsible of the disease has been identified as yet. Thus, experimental models that exhibit the same complex interactions are needed for testing various mechanisms and for assessing the carcinogenic potential of given chemicals. Rodent mammary carcinomas represent such a model to a great extent because, in these species, mammary cancer is a multistep complex process that can be induced by either chemicals, radiation, viruses, or genetic factors. Long-term studies in rodent models have been particularly useful for dissecting the initiation, promotion, and progression steps of carcinogenesis. The susceptibility of the rodent mammary gland to develop neoplasms has made this organ a unique target for testing the carcinogenic potential of specific genotoxic chemicals and environmental agents. Mammary tumors induced by indirect- or direct-acting carcinogens such as 7, 12-dimethlbenz(a)anthracene or N-methyl-N-nitrosourea are, in general, hormone dependent adenocarcinomas whose incidence, number of tumors per animal, tumor latency, and tumor type are influenced by the age, reproductive history, and endocarinologic milieu of the host at the time of carcinogen exposure. Rodent models are informative in the absence of human data. They have provided valuable information on the dose and route of administration to be used and optimal host conditions for eliciting maximal tumorigenic response. Studies of the influence of normal gland development on the pathogenesis of chemically induced mammary carcinomas have clarified the role of differentiation in cancer initiation. Comparative studies with the development of the human breast and the pathogenesis of breast cancer have contributed to validate rodent-to-human extrapolations. However, it has not been definitively established what type of information is necessary for human risk assessment, whether currently toxicity testing methodologies are sufficient for fulfilling those needs, or whether treatment-induced tumorigenic responses in rodents are predictive of potential human risk. An alternative to the traditional bioassays are mechanism-based toxicology and molecular and cellular approaches, combined with comparative in vitro systems. These approaches might allow the rapid screen of chemicals for setting priorities for further studies to determine the dose-response relationship for chemical effects at low doses, to assess effects other than mutagenesis and/or tumorigenesis, or to establish qualitative and quantitative relationships of biomarkers to toxic effects. Until there is enough information on the predictive value of mechanism-based toxicology for risk assessment, this approach should be used in conjunction with and validated by the traditional in vivo long-term bioassays.

Animals↗
PubMed1996

A profile of medically serious suicide attempts.

BACKGROUND: This study identified factors associated with medically serious suicide attempts (requiring medical hospitalization). METHOD: Demographic information, current psychiatric mental state, suicide attempt and psychiatric history characteristics, and DSM-IV diagnoses were compared between 65 patients hospitalized for a medically serious suicide attempt (MSSA) and 32 patients seen in the emergency room for suicide attempt but not medically hospitalized (NMSSA). RESULTS: Those with MSSAs had a higher rate of substance-induced mood disorder (but not substance abuse or dependence), while those with NMSSA had more attempts, more years since first attempt, and a higher rate of sexual and physical abuse, traumatic life events, borderline personality disorder, and bipolar disorder. CONCLUSION: Substance-induced mood disorder is an important diagnosis in the evaluation of suicidal patients. The vulnerability of mood effects caused by substance abuse may lead to a more serious suicide attempt despite less extensive psychiatric problems. The most important early psychiatric intervention may be the immediate recognition and aggressive treatment of an individual's affective and substance use disorders.

Bipolar Disorder↗
PubMed1995

Identification of 4-(N,N-dipropylamino)benzaldehyde as a potent, reversible inhibitor of mouse and human class I aldehyde dehydrogenase.

As the physiologic roles for the different classes of aldehyde dehydrogenase (ALDH) enzymes are elucidated, the identification of specific, reversible inhibitors becomes of great pharmacologic interest. Previous structure-function studies identified dialkylamino substituted benzaldehyde compounds as a novel class of reversible inhibitors of class I ALDH. To examine further structural requirements for inhibition, we tested a series of 4-(N,N-dialkylamino)benzaldehyde analogs as inhibitors of propanal oxidation by mouse liver and human erythrocyte class I ALDH. 4-(N,N-dipropylamino)benzaldehyde (DPAB) was identified as the most potent, reversible inhibitor of propanal oxidation by class I ALDH in spectrophotometric enzyme assays. In kinetic studies, DPAB showed mixed-type inhibition with respect to the aldehyde substrates propanal, phenylacetaldehyde, benzaldehyde, and aldophosphamide. DPAB exhibited uncompetitive inhibition with respect to the cofactor NAD. Inhibition constants (Ki) for DPAB, estimated from Dixon plots, were 10 nM (propanal) and 77 nM (phenylacetaldehyde) for mouse ALDH and 3 nM (propanal) and 70 nM (phenylacetaldehyde) for human ALDH. These Ki values are 100-fold lower than those reported for class I specific inhibitors. At low (< 1 microM) DPAB concentrations, inhibition of propanal and aldophosphamide oxidation was > 75%, whereas inhibition of benzaldehyde (32%) and phenylacetaldehyde (19%) oxidation was reduced markedly. These results indicate that DPAB exhibits potent, reversible inhibition of mouse and human class I ALDH. The degree of inhibition was highly dependent on the structure of the aldehyde substrate.

Acetaldehyde↗
PubMed1995

Collaborative management to achieve treatment guidelines. Impact on depression in primary care.

OBJECTIVE: To compare the effectiveness of a multifaceted intervention in patients with depression in primary care with the effectiveness of "usual care" by the primary care physician. DESIGN: A randomized controlled trial among primary care patients with major depression or minor depression. PATIENTS: Over a 12-month period a total of 217 primary care patients who were recognized as depressed by their primary care physicians and were willing to take antidepressant medication were randomized, with 91 patients meeting criteria for major depression and 126 for minor depression. INTERVENTIONS: Intervention patients received increased intensity and frequency of visits over the first 4 to 6 weeks of treatment (visits 1 and 3 with a primary care physician, visits 2 and 4 with a psychiatrist) and continued surveillance of adherence to medication regimens during the continuation and maintenance phases of treatment. Patient education in these visits was supplemented by videotaped and written materials. MAIN OUTCOME MEASURES: Primary outcome measures included short-term (30-day) and long-term (90-day) use of antidepressant medication at guideline dosage levels, satisfaction with overall care for depression and antidepressant medication, and reduction in depressive symptoms. RESULTS: In patients with major depression, the intervention group had greater adherence than the usual care controls to adequate dosage of antidepressant medication for 90 days or more (75.5% vs 50.0%; P < .01), were more likely to rate the quality of the care they received for depression as good to excellent (93.0% vs 75.0%; P < .03), and were more likely to rate antidepressant medications as helping somewhat to helping a great deal (88.1% vs 63.3%; P < .01). Seventy-four percent of intervention patients with major depression showed 50% or more improvement on the Symptom Checklist-90 Depressive Symptom Scale compared with 43.8% of controls (P < .01), and the intervention patients also demonstrated a significantly greater decrease in depression severity over time compared with controls (P < .004). In patients with minor depression, the intervention group had significantly greater adherence than controls to adequate dosage of antidepressant medication for 90 days or more (79.7% vs 40.3%; P < .001) and more often rated antidepressant medication as helping somewhat to helping a great deal (81.8% vs 61.4%; P < .02). However, no significant differences were found between the intervention and control groups in the percentage of patients who were satisfied with the care they received for depression (94.4% vs 89.3%), in the percentage who experienced a 50% or more decrease in depressive symptoms, or in the decrease of depressive symptoms over time. CONCLUSION: A multifaceted intervention consisting of collaborative management by the primary care physician and a consulting psychiatrist, intensive patient education, and surveillance of continued refills of antidepressant medication improved adherence to antidepressant regimens in patients with major and with minor depression. It improved satisfaction with care and resulted in more favorable depressive outcomes in patients with major, but not minor, depression.

Adult↗
PubMed1995

The etiopathogenesis of breast cancer prevention.

Breast cancer, the most frequent malignancy diagnosed in women, continues to increase in incidence in all industrialized nations. The fact that this disease becomes incurable once it has spread to regional or distant sites indicates that its complexity is beyond our present level of knowledge. A better understanding of the etiopathogenesis and biology of breast cancer is required in order to develop a rational basis for its prevention and therapy. The observation that early parity reduces the risk of developing breast cancer indicates that reproductive and hormonal conditions might play an important role in its prevention. The elucidation of the mechanisms mediating this protection requires the availability of adequate experimental models. The induction of rat mammary carcinomas with chemical carcinogens has proven to be useful for these purposes, especially since, in this model, full-term pregnancy or treatment of virgin rats with a placental hormone, human chorionic gonadotropin (hCG), prior to the administration of the carcinogen protects the mammary gland from tumor development. Since both pregnancy and hCG treatment induce differentiation of the mammary gland, this process is considered to be essential for the inhibition of the neoplastic process. The possibility of preventing breast cancer by treating young nulliparous females with hormones that mimic a full term pregnancy is of practical interest to the human female population, but it requires a thorough knowledge of the development of the human breast. Our studies indicate that the breast of postpubertal nulliparous women is composed of lobular structures reflecting different stages of development. Type I lobules are the most undifferentiated. Type 2 lobules evolve from the previous ones; they are composed of a higher number of ductular structures per lobule. They progress to lobules types 3 and 4, which are present in the breast during pregnancy and lactation. The type 1 lobule, considered to be the site of origin of ductal carcinomas, predominates in the breast of nulliparous women of all ages. In parous women, the type 3 lobule is the most frequent. Primary cultures derived from breast tissues composed of type 1 lobules express phenotypes of cell transformation not observed in cells derived from type 3 lobules. These data acquire relevance in the light that women with a history of early pregnancy are at a lower risk of developing breast cancer than nulliparous women, an effect attributed to differences in the degree of differentiation of the breast. Pregnancy furthers the differentiation of type 1 lobules to type 3, making them refractory to neoplastic transformation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Hormonally induced differentiation: a novel approach to breast cancer prevention.

Breast cancer, one of the most common neoplasms in women, develops more frequently in those who are nulliparous or late parous, who experience early menarche and late menopause and have a family history of breast cancer. Early parity, late menarche, early menopause, and hormone deprivation exert a protective effect. The mechanisms modulating these variations in malignancy susceptibility are not known. Epidemiologic and experimental studies indicate that malignancies develop in the mammary gland as a result of exposure to carcinogenic stimuli (i.e., chemical carcinogens, radiation). Neoplastic transformation requires that the gland be under specific developmental and age-related conditions at the time of exposure to such agents. In the rat, maximal susceptibility to neoplastic transformation is exhibited by the highly proliferating and undifferentiated gland of the young, virgin, intact females, whereas the fully differentiated gland of parous rats and virgin rats treated with the placental hormone human chorionic gonadotropin is protected from tumor development. Hormonally induced differentiation of the mammary gland is a novel approach to breast cancer prevention and therapy. The development of clinical protocols capitalizing on the protective effect of hormonal treatments mimicking pregnancy in humans is required to validate observations in experimental animal models, and to determine how they relate to epidemiologic and clinical findings. The feasibility of this approach is supported by the observed parallelism between humans and experimental models in both the site of cancer origin and the changes in breast development occurring with parity. Breast cancer initiates in terminal ductal lobular units or lobules type 1, the most undifferentiated structures frequently found in the breast of young nulliparous women.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Cardiovascular recovery from laboratory stress: biopsychosocial concomitants in older adults.

Although cardiovascular recovery may be important to long term cardiovascular health, its biopsychosocial correlates have received much less attention than the correlates of cardiovascular reactivity. Of the few studies that have examined recovery, fewer still have examined men and women over 60 yr of age. This study examined relationships of psychosocial factors (e.g. state anxiety, anger, avoidance coping, Type A behavior, etc.) with recovery in 186 older married men (n = 63) and women (n = 123) (mean age = 69.7 +/- 6.1 yr). Regressions were performed to explain recovery variability in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in response to emotional and cognitive tasks. In each analysis, we controlled for the effects of gender, type of task, reactivity to the task, and other important covariates. Individuals with slower recovery had higher scores on anxiety (for SBP, p < 0.03 and DBP, p < 0.01), higher scores on avoidance coping (for DBP and HR, p < 0.01), and lower scores on anger held in (for DBP, p < 0.01). Psychosocial factors may be important in explaining recovery in older adults.

Adaptation, Psychological↗
PubMed1995

Chronic fatigue: risk factors for symptom persistence in a 2 1/2-year follow-up study.

BACKGROUND: The prolonged disability of patients suffering from chronic fatigue may be due to sustaining factors that are independent of the cause and subject to intervention. This study reexamined a cohort of patients with chronic fatigue to define medical and psychiatric predictors of persistent symptoms. METHODS: Seventy-eight patients with chronic fatigue present for 6 months or more (not required to meet the Centers for Disease Control case definition for chronic fatigue syndrome [CFS]) completed a self-report, follow-up questionnaire to measure the overall improvement or worsening of their condition at a mean of 2.5 years after their initial examination. At the time of initial evaluation, patients underwent a structured psychiatric examination, physical examination, laboratory studies, and self-report measures of psychological distress and functional disability. The psychiatric examination queried the patient about 28 somatic symptoms that are separate from those associated with CFS. Discriminant analysis was used to determine which variables present at the initial examination were significant predictors of persistent symptoms and disability at 2.5 years. RESULTS: The factors most important at the time of initial presentation in predicting persistent illness were: (1) more than eight medically unexplained physical symptoms separate from those associated with CFS case definition; (2) lifetime history of dysthymia; (3) duration of chronic fatigue symptoms greater than 1.5 years; (4) less than 16 years of formal education; and (5) age older than 38 years. None of the results of the initial physical examination, or immunologic, general laboratory, or viral antibody measurements were significant in predicting persistence of symptoms. Recovery rates for those who met the criteria for CFS by either of two case definitions were lower than the rate of noncases, but the differences were not statistically significant. The five aforementioned variables formed a significant discriminative function, correctly classifying 78% of those who recovered and 74% of those with persistent symptoms. CONCLUSIONS: At initial examination, patients with chronic fatigue, more than eight medically unexplained physical symptoms (excluding symptoms in the case criteria for CFS), a lifetime history of dysthymic disorder, longer than 1.5 years of chronic fatigue, less than 16 years of formal education, and who were older than 38 years were the most likely to have persistence of symptoms of chronic fatigue at the 2.5-year follow-up.

Adult↗
PubMed1995

Psychiatric disorders in spouse caregivers of care recipients with Alzheimer's disease and matched controls: a diathesis-stress model of psychopathology.

To test a diathesis-stress model of psychopathology, the authors examined the rates of current and lifetime psychiatric disorders in 82 spouse caregivers of Alzheimer's disease (AD) patients and 86 demographically matched controls. Caregivers and controls did not differ in the prevalence of disorders before the onset of care recipients' AD (or during a similar time period for the controls); caregivers experienced more depressive-anxiety disorders after the onset of patient's AD than controls. This study strongly supported the 3 key components of a diathesis-stress interaction. First, caregivers with a psychiatric history prior to the onset of patient's AD were more likely than caregivers with no history to receive a diagnosis after the onset of AD. Second, a similar relationship existed for controls. Finally, caregivers with a psychiatric history were more likely to experience a recurrence after the onset of AD than controls with a psychiatric history. These findings indicate that the diathesis of psychiatric history and the stress of caregiving interact, resulting in the observed group differences in the prevalence of psychiatric disorders.

Aged↗
PubMed1995

Plasma lipids and their relationships with psychosocial factors in older adults.

Correlations of psychosocial factors (e.g., anger, avoidance coping, Type A behavior) with plasma lipid levels have been observed primarily in men younger than 60 years of age. This study examined these relationships in two groups of older women and men--spouse caregivers of individuals with Alzheimer's disease (n = 98) and controls (n = 91) group-matched for age and gender. Regression analyses determined whether psychosocial variables could explain variability in plasma lipids beyond relevant covariates. Covariates examined were gender, age, alcohol intake, smoking, body mass index, cardiovascular medications, diet (saturated fat), exercise, and estrogen use. Even with statistical controls, combinations of anger held-in, Type A behavior, anger-out, controlled anger, avoidance coping, and caregiving status explained significant variability in triglycerides (TG), high-density lipoproteins (HDLC), and low-density lipoproteins (LDLC). Male caregivers had higher TG and lower HDLC values than male controls. Results are discussed in the context of current thinking in the health psychology of aging.

Adaptation, Psychological↗
PubMed1995

Cathepsins D, B and L in breast carcinoma and in transformed human breast epithelial cells (HBEC).

An increased expression of lysosomal enzymes, cathepsin (Cat) D, Cat B and Cat L, was observed in various human tumours and after in vitro cell transformation. To establish possible co-ordination in their expression, all three cathepsins were determined in human breast tumours and in transformed human breast epithelial cells (HBEC). In breast carcinoma (n = 120) all three cathepsins, determined immunochemically and by enzymatic activity, were increased compared to normal breast tissues. The activities, correlated with the corresponding protein masses for Cat D (r = 0.77, p < 0.01), but not for Cat B and Cat L. Significant increase in Cat B activity was observed in stage II compared to stage I tumours, and Cat L activity in stage III compared to stage II tumours, but no significant correlation of cathepsin protein with tumour stage (TNM) was established. No significant correlation between Cat D and the cysteine cathepsins B and L was observed. Similarly, Cat D, Cat B and Cat L levels did not correlate in the in vitro system, e.g. in the five transformed HBEC, such as evolved after dimethylbenz(a)anthracene treatment and c-Has-ras oncogene transfection of diploid MCF-10F cell line (Calaf et al., 1993). Transformed cells showed increased anchorage-independent growth and invasive capability (MCF-10 < MCF-10FTras < D3 < D3-1 < D3-1Tras). The intracellular level of Cat D was not related to cell invasiveness, while total cellular Cat B and Cat L increased 13 fold and 4 fold, respectively, in the most invasive cell line, D3-1Tras compared to MCF-10F.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The 13q- syndrome: the molecular definition of a critical deletion region in band 13q32.

Patients with interstitial deletions of the long arm of chromosome 13 may have widely varying phenotypes. From cytogenetic analysis, we have postulated that there is a discrete region in 13q32 where deletion leads to a syndrome of severe malformations, including digital and brain anomalies. To test this hypothesis at the molecular level, we have studied the deletions in 17 patients; 5 had severe malformations, while the remaining 12 had only minor malformations. Our results indicate that the deletions in the severely affected patients all involve an overlapping region in q32, while the deletions in the mildly affected patients include some, but not all, of this overlapping region. Our findings are consistent with the hypothesis that the severely malformed 13q- phenotype results from the deletion of a critical region in 13q32. This region is presently defined as lying between D13S136 and D13S147 and is on the order of 1 Mb in size.

Abnormalities, Multiple↗
PubMed1995

The effects of hyaluronidase on local anesthesia: a prospective, randomized, controlled, double-blind study.

Hyaluronidase, an enzyme that breaks down intercellular cement, has been advocated as an additive to local anesthetics because it allows injected solutions to spread and penetrate tissues. Because epinephrine is commonly used in conjunction with local anesthetics, the combined effects of both hyaluronidase and epinephrine were studied in a prospective, controlled, double-blind manner. The forearms of volunteers ranging in number from 15 to 23 were injected with 0.5 ml of lidocaine to which graded doses of hyaluronidase and epinephrine had been added. At various intervals after injection, the areas of anesthesia were measured. From these data, the time to reach peak area of anesthesia (onset), the size of the peak area of anesthesia, and the time until disappearance of anesthesia (duration) were computed and analyzed. We found that epinephrine has a more profound effect on the onset, area, and duration of anesthesia than hyaluronidase. Epinephrine delayed the time to reach peak area of anesthesia (onset) relative to lidocaine alone more than hyaluronidase (0.28 h versus 0.04 h). When both agents were used together, the effect was subtractive (0.28-0.04 = 0.24 h, compared with 0.22 h observed). This suggests a negative interaction (inhibition) because hyaluronidase decreased the epinephrine effect by 21 percent. Concerning the size of peak area of anesthesia, epinephrine increased the area relative to lidocaine alone more than hyaluronidase (626 versus 221 mm2). When both agents were used together, the effect was additive (626 + 221 = 847 mm2, compared with 848 mm2 observed). This suggests that the two agents acted independently of each other in relation to area of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Polypeptide pattern of human breast epithelial cells following human chorionic gonadotropin (hCG) treatment.

Numerous attempts have made to describe the particular protein pattern of malignant cells by using high resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The placental hormone human chorionic gonadotropin (hCG) inhibits tumor initiation and progression in experimental animals and has an inhibitory effect on the proliferation of human breast epithelial cells (HBEC) in vitro. The inhibitory effect on the immortalized HBEC MCF-10F is accompanied by the immunocytochemical expression of inhibin alpha and beta subunits by treated cells. With the purpose of clarifying the molecular mechanisms involved in this effect, the pattern of protein synthesis and mRNA were studied by 2-D PAGE in the immortalized HBEC MCF-10F cells treated in vitro 1001U for 24 h. The effect of hCG treatment on the synthesis of MCF-10F cells was monitored by labeling both control and treated cells with [S35]methionine and separation by 2-D PAGE. At least 11 proteins were preferentially synthesized and five specific polypeptides were decreased in hCG treated cells in comparison with controls. The hCG induced at least four new mRNAs which encoded protein in the molecular mass range of 24-72 kDa. It also increased the expression of at least six mRNAs and reduced the expression of least four mRNAs in comparison with control cells. The hCG-treated cells actively synthesized a 33-kDa polypeptide which was not present in control cells. The nature of this hCG-inducible 33 kDa protein elucidated by immunoprecipating [S35]methionine-labeled proteins with antisera directed against rat inhibin subunit alpha and beta b.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast↗
PubMed1994

Allele loss and point mutation in codons 12 and 61 of the c-Ha-ras oncogene in carcinogen-transformed human breast epithelial cells.

There is significant evidence that the ras oncogene plays a role in experimental mammary carcinogenesis; the evidence in human breast cancer, however, is more limited. We induced the expression of transformation phenotypes in the human breast epithelial cell line MCF-10F with the chemical carcinogens 7,12-dimethylbenz[a]anthracene, N-methyl-N-nitrosourea, N-methyl-N-nitro-N'-nitrosoguanidine, and benzo[a]pyrene. This work was designed to clarify whether chemically induced neoplastic transformation correlates with alterations in the ras gene. MCF-10F cells have two c-Ha-ras alleles, identified by 1.0-kb and 1.2-kb restriction fragments. Treatment with carcinogens resulted in the loss of one of the alleles (1.0 kb). Polymerase chain reaction-amplified DNA from all carcinogen-treated cells was analyzed for point mutations in c-Ha-ras at codons 12 and 61. All of the carcinogens induced a mutation of the remaining allele at the first position of codon 12 (GGC-->AGC). Another frequent mutation occurred at the first position of codon 61 (CAG-->GAG). The changes in c-Ha-ras were associated with the emergence of colony formation in agar-methocel, but no specific changes in this gene correlated with the emergence of invasiveness or tumorigenesis, indicating that other genes may be involved in the process.

Adult↗