Factors associated with non-participation in a physical activity promotion trial.

BACKGROUND: Non-participation can bias outcome in intervention studies of physical activity. OBJECTIVES: To compare characteristics, knowledge and attitudes to physical activity in participants and non-participants of a physical activity intervention trial in primary care. STUDY DESIGN: Cross-sectional survey. METHODS: Patients aged 40-64 years were recruited opportunistically during surgery visits in an inner city general practice in Newcastle upon Tyne, UK. Attitudes to physical activity, views of its health benefits, and barriers to participation were elicited in interviews with participants, and by postal questionnaire from non-participants. Data held by general practitioners were used to compare anthropometry and lifestyle between groups. RESULTS: Of 842 eligible patients, 276 (33%) refused outright (non-volunteers) and 566 volunteered for the intervention study, of which 353 (42%) attended a baseline assessment and 213 (25%) subsequently defaulted. The initial refusal rate was higher amongst men, smokers and those with addresses in more deprived areas. The response rate to the postal survey of non-volunteers was 45%. Compared with participants, the non-volunteers were more likely to be an adult carer and to report poorer health, and were less likely to have had higher education or to have children living at home. Far more non-volunteers considered that they already did enough exercise to maintain health. Non-volunteers had slightly less knowledge of the benefits of physical activity; attached far less importance to it in maintaining health; were more likely to cite 'fear of leaving their home unattended', 'do not enjoy exercise' and 'poor health' as barriers to exercise; and were less likely to cite 'no one to exercise with' as a barrier to exercise. CONCLUSION: Recruitment of 'hard to engage' individuals requires careful phrasing of the message to focus on their personal goals and to address gaps in their knowledge about physical activity and the principal barriers they perceive. Differential uptake across population subgroups could lead to a widening of health inequalities.

Assessment in vitro of a novel therapeutic strategy for glioma, combining herpes simplex virus HSV1716-mediated oncolysis with gene transfer and targeted radiotherapy.

Genetically engineered herpes simplex virus ICP34.5 null mutants replicate only in dividing cells and have shown potential for the treatment of malignant disease, including glioma. Phase I trials have demonstrated the safety of these viruses in various clinical settings but it is envisaged that for full efficacy they will be used in combination with other therapeutic modalities. To enhance virus-induced tumour cytotoxicity, we have engineered an ICP34.5 null mutant (HSV1716) of HSV1 which expresses the noradrenaline transporter gene (NAT). This virus is designated HSV1716/NAT. We have shown previously that introduction of the NAT gene into a range of tumour cells, via plasmid-mediated transfection, conferred the capacity for active uptake of the radiopharmaceutical [131I]MIBG and resulted in dose-dependent toxicity. In this study, combination therapy utilising HSV1716/NAT and [131I]MIBG was assessed in vitro by the MTT assay. We demonstrate that the NAT gene, introduced by HSV1716/NAT into cultured glioma cells, was expressed 1 h after viral infection, enabling active uptake of [131I]MIBG. The combination of viral oncolysis and induced radiopharmaceutical uptake resulted in significantly enhanced cytotoxicity compared to either agent alone and the response was dose- and time-dependent. These studies show that the combination of oncolytic HSV therapy with targeted radiotherapy has the potential for effective tumour cell kill and warrants further investigation as a treatment for malignant glioma.

Up-regulation of a growth arrest and DNA damage protein (GADD34) in the ischaemic human brain: implications for protein synthesis regulation and DNA repair.

GADD34 is a growth arrest and DNA damage inducible gene up-regulated in response to DNA damage, cell cycle arrest and apoptosis. It is thought that GADD34 may play a crucial role in cell survival in ischaemia. GADD34 expression was assessed immunohistochemically in post-mortem human hippocampal tissue obtained from patients surviving for defined periods (0-24 h; 24 h-7 days) after a cardiac arrest and in age-matched control subjects. In control brain, cytoplasm staining in GADD34 immunopositive cells was faint but present throughout the hippocampus and cortex. There was minimal change in GADD34 expression in the group surviving 0-24 h after cardiac arrest. However GADD34 immunostaining was markedly increased in selectively vulnerable regions in the 24 h-7 day survival group. Increased GADD34 staining was present in ischaemic neurones and in some morphologically normal neurones after cardiac arrest. Extensive ischaemic damage was found to correlate with elevated GADD34 immunostaining in the CA1 layer of the hippocampus (**P < 0.0016). In addition, GADD34 was found to colocalize with proliferating cell nuclear antigen in some neurones. The up-regulation of GADD34 in response to global ischaemia in the human brain plus its influence on protein synthesis and DNA repair suggests that this protein may have the potential to influence cell survival.

HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival.

Following standard treatment, the prognosis remains poor in patients with high-grade glioma and new therapies are urgently required. Herpes simplex virus 1716 (HSV1716) is an ICP34.5 null mutant that is selectively replication competent and shown to be safe and to replicate following injection into high-grade glioma. We demonstrate that following surgical resection, HSV1716 is safe when injected into the brain adjacent to excised tumour. In all, 12 patients with recurrent or newly diagnosed high-grade glioma underwent maximal resection of the tumour. HSV1716 was injected into eight to 10 sites around the resulting tumour cavity with the intent of infecting residual tumour cells. As clinically indicated, patients proceeded to further radiotherapy or chemotherapy. There has been no clinical evidence of toxicity associated with the administration of HSV1716. Longitudinal follow-up has allowed the assessment of overall survival compared to that of similar patients not treated with HSV1716. Three patients remain alive and clinically stable at 15, 18 and 22 months postsurgery and HSV1716 injection. Remarkably, the first patient in the trial, who had extensive recurrent disease preprocedure, is alive at 22 months since injection of HSV1716 and 29 months since first diagnosis. Imaging has demonstrated a reduction of residual tumour over the 22-month period despite no further medical intervention since the surgery and HSV1716 injection. In this study, we demonstrate that on the basis of clinical observations, there has been no toxicity following the administration of HSV1716 into the resection cavity rim in patients with high-grade glioma. The survival and imaging data, in addition to the lack of toxicity, give us confidence to proceed to a clinical trial to demonstrate efficacy of HSV1716 in glioma patients.

HSV1716 persistence in primary human glioma cells in vitro.

HSV1716 is a selectively replication competent mutant of herpes simplex virus which is in trial in glioma patients. We have demonstrated that HSV1716 is non-toxic when delivered into tumour or into brain adjacent to tumour, yet replicates within tumour cells. Tumour tissue, from one patient treated 2.5 years previously with intra-tumoural HSV1716, was put into culture. The cultured cells were shown to be glial in origin with no evidence of residual HSV1716. These cells were subsequently infected at a MOI of 0.1 with either HSV1716 or wild-type HSV17(+). The HSV17(+) infected cells were completely rounded up or lysed within 72 h. Although the cells supported HSV1716 replication and also became rounded or lysed, a proportion (approximately 20%) remained viable. These cells continued to divide and shed low levels of HSV1716 up to 31 days after infection when there was evidence of rapid virus replication resulting in complete cell lysis. These data demonstrate that HSV1716 can 'persist' in human glioma cells at least in vitro and gives credence to the possibility that in tumours in vivo a similar phenomenon may take place. If this were the case, then HSV1716 has the potential to kill tumour cells over a prolonged period of time.

Specific expression of the cell cycle regulation proteins, GADD34 and PCNA, in the peri-infarct zone after focal cerebral ischaemia in the rat.

Cell cycle proteins play key roles in cell survival or death under pathological conditions. Expression of growth arrest and DNA damage-inducible protein, GADD34 and proliferating cell nuclear antigen (PCNA) have been investigated in the core and peri-infarct zone at 2 and 24 h after middle cerebral artery occlusion (MCAO). At these times after MCAO, numerous GADD34-positive cells were present, particularly in the peri-infarct zone (e.g. 24 +/- 4 and 52 +/- 6 immunopositive cells/0.25 mm2 at 2 and 24 h, respectively, in cortex). PCNA-immunopositive cells were barely detectable in the peri-infarct zone at 2 h; however, numerous PCNA-immunopositive cells were present in this zone by 24 h (0.7 +/- 0.3 and 10.6 +/- 1.5 immunopositive cells/0.25 mm2, respectively) as well as in the adjacent cortex and in the contralateral cingulate cortex. Most GADD34-immunopositive cells coexpressed the neuronal marker Neu-N with a smaller number coexpressing the microglial marker, Mrf-1. Evidence of morphologically 'abnormal' and 'normal' GADD34 immunopositive neurons was found within the peri-infarct zone. The majority of PCNA immunopositive cells were Mrf-1 positive with a smaller number Neu-N positive. Double-labelling revealed colocalization of GADD34 and PCNA in some cells within the peri-infarct zone and in the ependymal cells lining the ventricles. The presence of GADD34 and PCNA in a key anatomical location pertinent to the evolving ischaemic lesion indicates that GADD34, either alone or in combination with PCNA, has the potential to influence cell survival in ischaemically compromised tissue.

The potential for efficacy of the modified (ICP 34.5(-)) herpes simplex virus HSV1716 following intratumoural injection into human malignant glioma: a proof of principle study.

We have previously demonstrated the safety of intratumoural administration of the selectively replication-competent herpes simplex virus mutant HSV1716 in patients with high-grade glioma (HGG). Here we show its potential for efficacy by demonstrating that the virus survives and replicates when injected into the tumours of patients. Since HSV replication is a cytolytic process it must result in tumour cell killing. Twelve patients with biopsy-verified HGG received an intratumoural injection of 10(5) plaque-forming units (p.f.u.) of HSV1716. Four to 9 days after inoculation, tumours were removed and assayed for evidence of viral replication. In two patients, HSV1716, in excess of the input dose was recovered from the injection site. HSV DNA was detected by PCR at the sites of inoculation in 10 patients and at distal tumour sites in four. HSV-specific antigen was detected in tumour tissue from two patients. In five patients an immunological response to HSV1716, as detected by changes in levels of IgG and IgM, was demonstrated. This study demonstrates that HSV1716 replicates in HGG without causing toxicity in both HSV-seropositive and -seronegative patients.

Smoking and alcohol consumption in a UK Chinese population.

Little research has been conducted on health in Chinese communities in the UK and there are few representative data on smoking, alcohol consumption or other aspects of lifestyle. We undertook a cross sectional population-based study of 380 Chinese and 625 European men and women aged 25 to 64 y, using self-completion and interview questionnaires in Newcastle upon Tyne, UK between 1991 and 1995. We measured self-reported prevalence of cigarette smoking, number of cigarettes smoked per week and age at starting smoking; self-reported prevalence of alcohol consumption and units of alcohol consumed per week. In age-adjusted comparisons smoking was less common in Chinese (24%) than European men (35%) (P=0.00002) and among Chinese (1%) compared with European women (33%) (P<0.00001). Number of cigarettes smoked was similar among Chinese and European male smokers. Median age at starting smoking was higher among Chinese (18.5 y) compared with European men (15 y) (P=0.00001). Smoking was commonest in older Chinese and in younger Europeans. The prevalence of alcohol consumption was lower among Chinese (63%) than European men (93%) (P<0.00001) and among Chinese (29%) compared to European women (89%) (P<0.00001). Median alcohol consumption was significantly lower among Chinese (2 units/week) than European men (16 units/week) (P<0.00001), and among Chinese (1 unit/week) compared to European women (6 units/week) (P<0.00001). Among those who drank alcohol, Chinese men were less likely to drink above recommended limits than European men (1% vs 39%; P<0.00001). Chinese men and women currently have relatively favourable patterns of smoking compared to European adults in Newcastle. Average alcohol consumption among Chinese who drink is lower than among Europeans, and a substantial proportion of the Chinese population in Newcastle drink no alcohol. Patterns of health related behaviour should be tracked over time in ethnic minority populations to identify changes that pose risk to health and which deserve appropriate intervention.

Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma.

The herpes simplex virus (HSV) ICP34.5 null mutant 1716 replicates selectively in actively dividing cells and has been proposed as a potential treatment for cancer, particularly brain tumours. We present a clinical study to evaluate the safety of 1716 in patients with relapsed malignant glioma. Following intratumoural inoculation of doses up to 10(5) p.f.u., there was no induction of encephalitis, no adverse clinical symptoms, and no reactivation of latent HSV. Of nine patients treated, four are currently alive and well 14-24 months after 1716 administration. This study demonstrates the feasibility of using replication-competent HSV in human therapy.

A comparison of proxy measures of abdominal obesity in Chinese, European and South Asian adults.

AIMS: To assess whether four proxy measures of abdominal obesity (waist circumference; waist-to-hip ratio (WHR); waist-to-height ratio and C index, a measure of body shape) were uniformly associated with features of the metabolic syndrome (triglycerides, high density lipoprotein (HDL) cholesterol, 2-h glucose) in three ethnic groups. METHODS: Anthropometric and biochemical data were collected in 629 Europeans (320 men, 309 women), 380 Chinese (183 men, 197 women) and 597 South Asians (275 men, 322 women) aged 25-64 years in Newcastle upon Tyne, UK. Linear regression models were used to determine whether relationships differed between ethnic groups. RESULTS: Linear regression analysis showed that most proxy measures of abdominal obesity were associated with features of the metabolic syndrome. There were significant interactions between WHR and ethnicity and C index and ethnicity in the relationship with log triglycerides when comparing European and Chinese women. Interactions existed between all proxy measures and ethnicity in the relationship with log triglycerides and HDL cholesterol when comparing European and South Asian women. In men, interactions between ethnicity and waist circumference, WHR and C index when comparing Europeans and South Asians, and between ethnicity and WHR and C index when comparing South Asian and Chinese for log 2-h glucose were significant (P < 0.001). All interactions remained significant when differences in smoking, alcohol and physical activity were taken into account. CONCLUSIONS: Not all the proxy measures of abdominal obesity were consistently related to features of the metabolic syndrome across the ethnic groups studied. However, waist circumference and waist to height ratio were the most consistent and WHR the least when comparing across the ethnic groups.

The Newcastle exercise project: a randomised controlled trial of methods to promote physical activity in primary care.

OBJECTIVE: To evaluate the effectiveness of combinations of three methods to promote physical activity. DESIGN: Randomised controlled trial. Baseline assessment with post-intervention follow up at 12 weeks and 1 year. SETTING: One urban general practice, 1995-7. PARTICIPANTS: 523 adults aged 40 to 64 years, randomised to four intervention groups and a control group. INTERVENTIONS: Brief (one interview) or intensive (six interviews over 12 weeks) motivational interviewing based on the stages of change model of behaviour change, with or without financial incentive (30 vouchers entitling free access to leisure facilities). MAIN OUTCOME MEASURES: Physical activity score; sessions of moderate and vigorous activity in the preceding four weeks. RESULTS: Response rate was 81% at 12 weeks and 85% at one year. More participants in the intervention group reported increased physical activity scores at 12 weeks than controls (38% v 16%, difference 22%, 95% confidence interval for difference 13% to 32%), with a 55% increase observed in those offered six interviews plus vouchers. Vigorous activity increased in 29% of intervention participants and 11% of controls (difference 18%, 10% to 26%), but differences between the intervention groups were not significant. Short term increases in activity were not sustained, regardless of intensity of intervention. CONCLUSIONS: The most effective intervention for promoting adoption of exercise was the most intensive. Even this did not promote long term adherence to exercise. Brief interventions promoting physical activity that are used by many schemes in the United Kingdom are of questionable effectiveness.

Heterogeneity of coronary heart disease risk factors in Indian, Pakistani, Bangladeshi, and European origin populations: cross sectional study.

OBJECTIVE: To compare coronary risk factors and disease prevalence among Indians, Pakistanis, and Bangladeshis, and in all South Asians (these three groups together) with Europeans. DESIGN: Cross sectional survey. SETTING: Newcastle upon Tyne. PARTICIPANTS: 259 Indian, 305 Pakistani, 120 Bangladeshi, and 825 European men and women aged 25-74 years. MAIN OUTCOME MEASURES: Social and economic circumstances, lifestyle, self reported symptoms and diseases, blood pressure, electrocardiogram, and anthropometric, haematological, and biochemical measurements. RESULTS: There were differences in social and economic circumstances, lifestyles, anthropometric measures and disease both between Indians, Pakistanis, and Bangladeshis and between all South Asians and Europeans. Bangladeshis and Pakistanis were the poorest groups. For most risk factors, the Bangladeshis (particularly men) fared the worst: smoking was most common (57%) in that group, and Bangladeshis had the highest concentrations of triglycerides (2.04 mmol/l) and fasting blood glucose (6.6 mmol/l) and the lowest concentration of high density lipoprotein cholesterol (0.97 mmol/l). Blood pressure, however, was lowest in Bangladeshis. Bangladeshis were the shortest (men 164 cm tall v 170 cm for Indians and 174 cm for Europeans). A higher proportion of Pakistani and Bangladeshi men had diabetes (22.4% and 26.6% respectively) than Indians (15.2%). Comparisons of all South Asians with Europeans hid some important differences, but South Asians were still disadvantaged in a wide range of risk factors. Findings in women were similar. CONCLUSION: Risk of coronary heart disease is not uniform among South Asians, and there are important differences between Indians, Pakistanis, and Bangladeshis for many coronary risk factors. The belief that, except for insulin resistance, South Asians have lower levels of coronary risk factors than Europeans is incorrect, and may have arisen from combining ethnic subgroups and examining a narrow range of factors.

Evidence for a slow time-scale of interaction for magnetic fields inhibiting tamoxifen's antiproliferative action in human breast cancer cells.

One critical biophysical feature of environmental-level magnetic field (MF) interactions with biological systems is the time-scale of interaction. A recently proposed fast/slow hypothesis states that a fast mechanism can only sense the instantaneous absolute value of the MF, and that a slow mechanism is potentially capable of sensing features such as frequency and relative orientation and magnitude of the field components. Here we applied the fast/slow hypothesis to a breast cancer model system: A 1.2 microT (rms), 60-Hz field inhibits tamoxifen's (TAM's) cytostatic action in MCF-7 cells via a MF interaction. We measured the growth of MCF-7 cells treated with TAM over 7 d, within different MFs: a sinusoidal, 60-Hz, 0.2-microT(rms) field; a sinusoidal, 60-Hz, 1.2-microT(rms) field; and a full-wave rectified version of the 1.2-microT(rms) sinusoidal field. A fast mechanism should not be able to distinguish between the latter two exposures. We observe that the rectified 1.2-microT field does not inhibit TAM's action, but that the 1.2-microT sinusoidal field does. Therefore, the 1.2-microT MF inhibition of TAM's cytostatic action operates via a relatively slow mechanism, and we predict that there exists a biologically dynamic complex capable of sensing a 1.2-microT, 60-Hz sinusoidal MF with an intrinsic time-scale of 17 ms or longer, the period of the 60-Hz applied field.

Comparison of the current WHO and new ADA criteria for the diagnosis of diabetes mellitus in three ethnic groups in the UK. American Diabetes Association.

The American Diabetes Association have recommended that the fasting plasma glucose level for the diagnosis of diabetes is lowered and that this becomes the main diagnostic test. We have used population-based data from three ethnic groups in Newcastle upon Tyne to examine the implications of this change. Data were available on 824 European (25-74 years), 375 Chinese (25-64 years), and 680 South Asian (25-74 years) subjects. All subjects apart from those reporting a prior diagnosis of diabetes underwent a standard 75 g oral glucose tolerance test (WHO criteria) which included the measurement of fasting glucose. The prevalence of diabetes was higher in all three ethnic groups using the new ADA criteria compared to the WHO criteria: 7.1% vs 4.8% in Europeans; 6.2% vs 4.7% in Chinese; and 21.4% vs 20.1% in South Asians. There was much variation in individuals categorized by the ADA and WHO criteria. Agreement between the two for the diagnosis of previously unknown diabetes was only moderate (kappa statistics 0.42 to 0.59). Thus in the populations studied the new criteria would increase the prevalence of diabetes in addition to classifying some individuals diabetic by current criteria as non-diabetic. It should be stressed however that diagnosis of the individual should not be based on a single test.

HSV Growth, Preparation, and Assay.

Whether herpes simplex virus (HSV) is viewed as a pathogen or as a model eukaryotic system, it is virtually certain that any experimental work will require the virus to be grown and assayed. The following chapter is therefore seen as the fundamental first step before embarking on more intellectually and technically challenging technology. Its importance should not however be underestimated. It never fails to surprize us that people who describe themselves as virologists have little understanding of the basic requirements needed to attain a contamination-free, high-titer, low particle:plaque-forming units (PFU) ratio, genetically pure virus stock.

The herpes simplex virus virulence factor ICP34.5 and the cellular protein MyD116 complex with proliferating cell nuclear antigen through the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34.

The herpes simplex virus (HSV) virulence factor ICP34.5, the mouse myeloid differentiation protein MyD116, and the hamster growth arrest and DNA damage protein GADD34 share a 63-amino-acid carboxyl domain which has significant homologies to otherwise divergent proteins. Here we report that both ICP34.5 and its cellular homolog MyD116 complex through the conserved domain with proliferating cell nuclear antigen. In addition, HSV infection induces a novel 70-kDa cellular protein detectable by antisera to both ICP34.5 and GADD34, demonstrating that this novel protein possesses homology with the 63-amino-acid conserved domain.

Identifying Chinese populations in the UK for epidemiological research: experience of a name analysis of the FHSA register. Family Health Services Authority.

There is a paucity of research on health in the UK Chinese community partly due to the difficulties of identifying and accessing study populations. For a survey of cardiovascular disease we aimed to identify and recruit all Chinese adults aged 25-64 y living in Newcastle-upon-Tyne, UK. One thousand, eight hundred and sixty-five potential subjects were identified using a variety of methods. Of the 1702 potential subjects identified from a name analysis of the 1991 FHSA register (FHSA group), 638 students in halls of residence were excluded and the remaining 1064 were invited to participate. Non-respondents were followed up. Of the 1064, 658 (65.5%) addresses were no longer valid, 21 (2%) were reclassified as non-Chinese and no contact was made with 18 individuals (1.6%). A further 163 subjects (non-FHSA group) came forward in response to publicity, giving a total of 530 Chinese actually identified in Newcastle. Three hundred and eighty subjects took part in the study. Compared to the 1991 Census, the recruitment procedure underestimated the total population size, particularly for men and younger ages. In the FHSA group, men were significantly more likely to be current drinkers, and women were more likely to smoke and have a lower educational attainment that the non-FHSA group. There were no other important differences in the distribution of CHD risk markers in the two groups. Our experience indicates that the FHSA register is suitable for identifying Chinese but should be used alongside other complementary methods to augment samples for ethnicity and health research.

Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK.

OBJECTIVE: To compare the prevalence of glucose intolerance (impaired glucose tolerance and diabetes), and its relationship to body mass index (BMI) and waist-hip ratio in Chinese and Europid adults. DESIGN: This was a cross sectional study. SETTING: Newcastle upon Tyne. SUBJECTS: These comprised Chinese and Europid men and women, aged 25-64 years, and resident in Newcastle upon Tyne, UK. MAIN OUTCOME MEASURES: Two hour post load plasma glucose concentration, BMI, waist circumference, and waist-hip ratio. METHODS: Population based samples of Chinese and European adults were recruited. Each subject had a standard WHO oral glucose tolerance test. RESULTS: Complete data were available for 375 Chinese and 610 Europid subjects. The age adjusted prevalences of glucose intolerance in Chinese and Europid men were 13.0% (p = 0.04). Mean BMIs were lower in Chinese men (23.8 v 26.1) and women (23.5 v 26.1) than in the Europids (p values < 0.001), as were waist circumferences (men, 83.3 cm v 90.8, p < 0.001; women, 77.3 cm v 79.2, p < 0.05). Mean waist-hip ratios were lower in Chinese men (0.90 v 0.91, p = 0.02) but higher in Chinese women (0.84 v 0.78, p < 0.001) compared with Europids. In both Chinese and Europid adults, higher BMI, waist circumference, and waist-hip ratio were associated with glucose intolerance. CONCLUSIONS: The prevalence of glucose intolerance in Chinese men and women, despite lower BMIs, is similar to or higher than that in local Europid men and women and intermediate between levels found in China and those in Mauritius. It is suggested that an increase in mean BMI to the levels in the Europid population will be associated with a substantial increase in glucose intolerance in Chinese people.

Environmental magnetic fields inhibit the antiproliferative action of tamoxifen and melatonin in a human breast cancer cell line.

We have previously reported that environmental-level magnetic fields (1.2 microT [12 milligauss], 60 Hz) block the growth inhibition of the hormone melatonin (10(-9) M) on MCF-7 human breast cancer cells in vitro. We now report that the same 1.2 microT, 60 Hz magnetic fields significantly block the growth inhibitory action of pharmacological levels of tamoxifen (10(-7) M). In biophysical studies we have taken advantage of Faraday's Law of Current Induction and tested whether the 1.2 microT magnetic field or the associated induced electric field is responsible for this field effect on melatonin and tamoxifen. We observe that the magnetic field component is associated with the field blocking effect on melatonin and tamoxifen function. To our knowledge the tamoxifen studies represent the first experimental evidence for an environmental-level magnetic field modification of drug interaction with human breast cancer cells. Together, these findings provide support to the theory that environmental-level magnetic fields can act to modify the action of a drug or hormone on regulation of cell proliferation. Melatonin and tamoxifen may act through different biological pathways to down-regulate cell growth, and further studies are required to identify a specific biological site of interaction for the 1.2 microT magnetic field.