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Recovery of auditory function and structure in the chick after two intense pure tone exposures.

Groups of neonatal chicks were examined in three experimental conditions that differed in the age and number of times they were exposed to a pure tone of 0.9 kHz at 120 dB SPL for 48 h. Several animals were exposed once at 2 or 16 days of age, while others were subjected twice to the above stimulus, first at 2 days and then at 16 days. Evoked potential measures of threshold shift, obtained at 0, 12 or 26 days post-exposure, were used to determine the degree of hearing loss and recovery. The average threshold loss in the mid-range frequencies was about 57 dB at 0 days for all three conditions. This level was reduced to about 15 dB in all three groups at 12 days of recovery, while in birds exposed once at 2 days, but allowed 26 days to recover, the post-exposure thresholds returned to pre-exposure levels. Scanning electron microscopic analysis of cochlear structure was conducted in groups of similarly exposed and recovered animals. Twelve days post-exposure, the structural analysis revealed regeneration of a single honeycomb-like tectorial membrane layer in both the once and twice-exposed cochleae. However, damage to, and repair of, the tectorial membrane after the second exposure revealed the production of a second honeycomb layer in about half the animals examined. The results indicated that chicks retain the capacity to repair receptor epithelium damage and recover considerably from hearing loss after multiple exposures to intense sound.

Acoustic Stimulation↗

Ambient UV, personal sun exposure and risk of multiple primary melanomas.

OBJECTIVE: Sun exposure is the main cause of melanoma in populations of European origin. No previous study has examined the effect of sun exposure on risk of multiple primary melanomas compared with people who have one melanoma. METHODS: We identified and enrolled 2,023 people with a first primary melanoma (controls) and 1,125 with multiple primary melanomas (cases) in seven centers in four countries, recorded their residential history to assign ambient UV and interviewed them about their sun exposure. RESULTS: Risk of multiple primary melanomas increased significantly (P<0.05) to OR=2.10 for the highest exposure quarter of ambient UV irradiance at birth and 10 years of age, to OR=1.38 for lifetime recreational sun exposure, to OR=1.85 for beach and waterside activities, to OR=1.57 for vacations in a sunnier climate, to OR=1.50 for sunburns. Occupational sun exposure did not increase risk (OR=1.03 for highest exposure). Recreational exposure at any age increased risk and appeared to add to risk from ambient UV in early life. CONCLUSIONS: People who have had a melanoma can expect to reduce their risk of a further melanoma by reducing recreational sun exposure whatever their age. The same is probably true for a person who has never had a melanoma.

Adolescent↗

Ultraviolet radiation abolishes cutaneous nerve stainings with two axon-specific antibodies in guinea-pig skin.

Cutaneous nerve fibers in guinea-pig skin were histochemically stained with two specific antibodies against different axonal proteins, a newly available protein gene product 9.5 and neuron-specific enolase. A semi-quantitative analysis revealed that the density of nerve fibers positive for either antibody was reversibly decreased following a single exposure to medium wave length ultraviolet (UVB) radiation and psoralen plus long wave ultraviolet (UVA) radiation (PUVA). UVA radiation alone did not markedly affect nerve fiber staining. The UVB/PUVA-induced nerve changes were augmented and prolonged following multiple exposures to UVB and PUVA. Nerve fiber staining was not altered by topical application of corticosteroids. Our findings suggest that both UVB and PUVA can alter the cutaneous innervation density.

Animals↗

Gasping is elicited by briefer hypoxia or ischemia following blockade of glycinergic transmission.

The 'switching model' for generation of respiratory rhythms holds that gasping represents the release of a rostral medullary pacemaker mechanism from the pontomedullary neuronal circuit that generates eupnea. In a perfused preparation of the decerebrate juvenile rat, exposure to ischemia or hypoxic-hypercapnia caused an alteration in integrated phrenic activity from the incrementing pattern of eupnea to the decrementing pattern of gasping. The time required to elicit gasping was not altered by multiple exposures to ischemia or hypoxic-hypercapnia. Furthermore, this time to gasping was not altered following addition to the perfusate of increasing concentrations of bicuculline or picrotoxin; both block GABA(A) receptors. Addition to the perfusate of strychnine, a glycine antagonist, significantly shortened the duration of ischemia or hypoxic-hypercapnia required to elicit gasping. These results support the concept that a loss of inhibitory glycinergic transmission is a critical factor in release of pacemaker mechanisms for gasping from the pontomedullary neuronal circuit for eupnea.

Animals↗

Sunlight and dysplastic nevus risk. Results of a clinic-based case-control study.

The dysplastic nevus (DN) is the most important risk factor and precursor for malignant melanoma. The authors compared the responses of 132 consecutive cases of DN, 186 consecutive cases of cutaneous melanoma, and 239 controls attending the same subspecialty clinic to questions regarding sun sensitivity, sun exposure, and other possible risk factors. Dysplastic nevus cases were younger than controls and were of a higher social class, as indicated by more years of formal education. Sun sensitivity (assessed by reported depth of tan after multiple exposures) was associated with both DN risk and melanoma risk after controlling for age and education in logistic regression analysis (P = 0.009 and 0.03, respectively), but for DN risk this association was nonlinear: the relative risks (versus deep tan) were 2.3 for average tanners, 2.8 for light tanners, and 1.6 for those who reported practically no tan. Sun exposure measures were not associated with DN risk after controlling for age and education, whether or not depth of tan was controlled in the analysis. These observations suggest a role for either sunlight or a trait linked with sun sensitivity in the development of dysplastic nevi.

Adult↗

Organ-specific hematopoietic changes induced by a recombinant human interferon-alpha in mice.

Interferon-alpha (IFN-alpha) is a naturally occurring cytokine that mediates numerous biological activities and has demonstrated therapeutic potential in a variety of malignancies. Encouraging activity against HIV-1 replication has also been observed with IFN-alpha in the treatment of AIDS, although hematotoxicity has been a frequently observed side effect. In addition, in vitro studies have suggested that IFN-alpha may function as a down-regulator of myelopoiesis. A recombinant hybrid of subtypes of human IFN-alpha, rHuIFN-alpha A/D, has antiviral activity in murine cells in vitro and in vivo. This study examines the effect of acute and subchronic exposure to rHuIFN-alpha A/D on hemopoietic and immune parameters in C57Bl/6 mice. IFN-alpha was administered ip at 0, 1000, 10,000, and 100,000 units/day for either 1 or 10 consecutive days. Many of the known effects of IFN-alpha in humans such as anemia, leukopenia, and thrombocytopenia were observed in mice following subchronic exposure, with the latter two effects also manifested following acute exposure. Further analysis showed that this leukopenia was not selective. Both splenic and bone marrow cells were examined following 10 days of dosing with the high dose of IFN-alpha. Lymphocytes were reduced in both compartments, while granulocytes were increased in both compartments. Bone marrow cells programmed to differentiate into granulocytes (CFU-G) were suppressed, while macrophage progenitors (CFU-M) were stimulated. Erythroid cells decreased in the marrow but increased in the spleen, suggesting that the microenvironment may play a significant role in the effect of IFN-alpha. The proliferative capacity of both B and T splenic lymphocytes was significantly suppressed in a dose-related fashion following multiple exposure to IFN-alpha. Clinically, IFN-alpha is most often given in multiple doses and the present data suggest that such a regimen is toxic to both erythroid and myeloid cells, as well as being immunotoxic to splenic B and T lymphocytes.

Alanine Transaminase↗

Aspirin pretreatment reduces ethanol withdrawal severity in a mouse model of binge drinking.

Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin, which inhibit prostaglandin (PG) synthesis, have a pronounced effect on a broad range of ethanol (EtOH) actions. Given this, it is somewhat surprising that NSAID treatment has not been found to alter major signs of ethanol withdrawal. To date, the only effect found has been indirect, that is, NSAID treatment reduces the efficacy of PG precursor administration in the treatment of ethanol withdrawal via the inhibition of PG formation. However, in those studies reporting negative results NSAID administration was delayed until EtOH withdrawal. Studies demonstrating NSAID-related attenuation of other actions of EtOH have typically employed a pretreatment paradigm in which NSAIDs are administered prior to, not after, ethanol exposure. Thus, it may be that the point in the ethanol exposure/withdrawal episode at which NSAIDs are administered could be crucial in determining their effects of the ethanol withdrawal syndrome. To address this issue, we employed a multiple-exposure "binge drinking" model. On each of 6 treatment days, male BALB/c mice were injected subcutaneously with either acetylsalicylic acid (ASA, 150 mg/kg) or the buffer vehicle, followed 1 h later by either ethanol (4.0 g/kg) or saline (0.9%) by gavage. Ethanol withdrawal severity, as measured by handling-induced convulsions, was determined 2, 4, 6, 8, 10, 12, and 24 h after EtOH gavage. ASA pretreatment was found to significantly reduce handling-induced convulsions in ethanol-intubated animals. In fact, the attenuation was of such a magnitude that the ASA-pretreated ethanol group did not significantly differ in withdrawal severity from non-ethanol-exposed controls. This effect was not likely due to ASA-related alterations in ethanol pharmacokinetics. These findings have relevance for the understanding of the basic mechanisms underlying ethanol dependence, as well as the potential role of PGs in this phenomenon.

Alcoholism↗

Allergic contact dermatitis.

Contact dermatitis is an inflammatory skin condition induced by exposure to an environmental agent. Eczema and dermatitis are used synonymously to denote a polymorphous pattern of skin inflammation characterized at least in its acute phase by erythema, vesiculation and pruritus. Substances responsible for contact dermatitis after single or multiple exposures are non protein chemicals, i.e. haptens, that induce skin inflammation through activation of innate skin immunity (irritant contact dermatitis) or both innate and acquired specific immunity (allergic contact dermatitis). The present review will focus on allergic contact dermatitis, a delayed-type hypersensitivity reaction, which is mediated by hapten-specific T cells. Recent advances in the pathophysiology of ACD have shown that the occurrence of ACD, as well as its magnitude and duration, is controlled by the opposite functions of CD8 effector T cells and CD4 regulatory T cells. From these studies ACD can be considered as a breakdown of cutaneous immune tolerance to haptens.

Dermatitis, Allergic Contact↗

Aqueous flare increase after light exposure in age-related macular degeneration.

An increase in anterior chamber flare is associated with many ocular conditions, including retinal diseases. We assessed anterior chamber flare in 18 patients (19 eyes) with exudative age-related macular degeneration using the Kowa flare-cell meter immediately before and 1 hour after exposure to 40 light flashes at a flash intensity of 300 W/s delivered with a Topcon fundus camera. Fourteen eyes showed a significant increase in flare 1 hour after light exposure (T = -3.452, p < 0.003, t-test). A second measurement in a subgroup of 10 patients exposed to 40 light flashes at a flash intensity of 36 W/s showed no significant change in flare 1 hour after light exposure. Multiple analysis of variance (two-way interaction) showed a highly significant difference between the two groups (F[1,27] = 8.66, p < 0.0066). We discuss possible mechanisms that may have produced these changes as well as implications of light exposure in various diagnostic and therapeutic settings.

Aqueous Humor↗

Effect of continuous versus multiple intermittent light exposures on rat retina.

The damaging effects of continuous light exposure to the albino rat retina have been well documented. However, the cumulative effects of multiple light exposures are not well defined. We therefore compared the retinal injury induced by a single 24 hour light exposure with that caused by three intermittent exposures of 8 hours each. Eight dark-adapted albino Lewis rats were exposed for 24 hours to green fluorescent light (490-580 nm) at an illuminance level of 175 foot-candles. A second group of 8 rats was exposed under similar conditions in three split doses of 8 hours each at intervals of 7 days between each exposure. Recovery was allowed in total darkness, and the animals were sacrificed 2 weeks following the last exposure. Retinal damage was assessed by morphometry and light and electron microscopy. Mild cumulative retinal injury, mostly in photoreceptor cells with relative sparing of the retinal pigment epithelium, was seen in the split dose group, while extensive damage involving photoreceptor cells and retinal pigment epithelium was noted in the group exposed continuously for 24 hours.

Animals↗

Increased bioaccumulation of urethane in CYP2E1-/- versus CYP2E1+/+ mice.

Urethane is a fermentation by-product and a potent animal carcinogen. Human exposure to urethane occurs through consumption of alcoholic beverages and fermented foods. Recently, CYP2E1 was identified as the primary enzyme responsible for the metabolism of [(14)C]carbonyl-labeled urethane. Subsequently, attenuation of urethane-induced cell proliferation and genotoxicity in CYP2E1-/- mice was reported. The present work compares the metabolism of single versus multiple exposures of CYP2E1-/- and CYP2E1+/+ mice to (14)C-ethyl-labeled urethane. Urethane was administered as a single 10 or 100 mg/kg gavage dose or at 100 mg/kg/day for 5 consecutive days. CYP2E1+/+ mice administered single or multiple doses exhaled 78 to 88% of dose as (14)CO(2)/day. CYP2E1-/- mice eliminated 30 to 38% of a single dose as (14)CO(2) in 24 h and plateaued after day 3 at approximately 52% of dose/day. The concentrations of urethane-derived radioactivity in plasma and tissues were dose-dependent, increased as a function of the number of doses administered, and were significantly higher in CYP2E1-/- versus CYP2E1+/+ mice. Whereas urethane was the main chemical found in the plasma and tissues of CYP2E1-/- mice, it was not detectable in CYP2E1+/+ mice. In conclusion, multiple dosing led to considerable bioaccumulation of urethane in mice of both genotypes; however, greater retention occurred in CYP2E1-/- versus CYP2E1+/+ mice. Furthermore, greater bioaccumulation of (14)C-ethyl-labeled than [(14)C]carbonyl-labeled urethane was observed in mice. Comparison of the metabolism of ethyl-versus carbonyl-labeled urethane was necessary for tracing the source of CO(2) and led us to propose for the first time that C-hydroxylation is a likely pathway of urethane metabolism.

Animals↗

Murine retroviral disease-enhancing effects of a pyrimidinone immunomodulator.

(B10.A x A/WySn)F1 mice, infected with the Friend virus (FV) complex, were used as a predictive therapeutic model for AIDS. These infected mice exhibit many of the viral and immunologic manifestations of AIDS. Bropirimine (2-amino-5-bromo-6-phenyl-4[3H]pyrimidinone, ABPP) is an immunomodulating compound which has been shown to inhibit other viral infections. Oral (per os treatment) dosages of ABPP ranging from 50 to 400 mg/kg/day for 3 days resulted in increased numbers of infectious centers in the infected mice and increased splenomegaly and percentage of Ig+ (B cells) in spleens of infected and uninfected mice. Decreased percentages of total Thy-1.2+ (total T) cells and L3T4+ (T-helper) cells were seen in both uninfected and infected mice and a slightly decreased percentage of Ly-2+ (T-suppressor/cytotoxic) cells was observed in spleens of the infected mice. No effect on Ly2+ cells in spleens of uninfected mice was found. Intraperitoneal injection, single or multiple, of 20-200 mg/kg ABPP prior to FV injection resulted in increased spleen weights but had no effect on numbers of infectious centers in the spleens or on FV antibody titers in the plasma. Intraperitoneal treatment of uninfected mice with ABPP resulted in slight or no changes in percentages of Thy-1.2+, L3T4+ and Ly-2+ cells. Mice receiving multiple exposures of ABPP had an increase in percentage of splenic B cells and a depressed response to the T cell mitogen PHA. Treatment with ABPP induced the production of interferon (IFN); however, a state of hyporesponsive IFN production was seen following multiple administrations of ABPP. These data suggest that the immunomodulator ABPP may have an enhancing effect on this retroviral disease.

Acquired Immunodeficiency Syndrome↗

Contact dermatitis II. Clinical aspects and diagnosis.

Contact dermatitis (CD) is an altered state of skin reactivity induced by exposure to an external agent. "Eczema" and "dermatitis" are often used synonymously to denote a polymorphic pattern of inflammation of the skin characterized, at least in its acute phase, by erythema, vesiculation and pruritus. Substances that induce CD after single or multiple exposures may be irritant or allergic in nature. The clinical presentation may vary depending on the identity of the triggering agent and the reactivity of the subject, but in all cases the lesions are primarily confined to the site of contact. According to the mechanism of elicitation, the following types of contact reactions may be distinguished: (1) allergic contact dermatitis (ACD); (2) irritant contact dermatitis (ICD); (3) phototoxic and photoallergic contact dermatitis, and (4) immediate type contact reactions. The present review will focus on allergic contact dermatitis. ACD is the clinical presentation of contact sensitivity in humans. The pathophysiology of the contact sensitivity reaction has been reviewed in a preceding issue of this journal [1].

Dermatitis, Allergic Contact↗

Risk assessment of opportunistic bacterial pathogens in drinking water.

This study was undertaken to examine quantitatively the risks to human health posed by heterotrophic plate count (HPC) bacteria found naturally in ambient and potable waters. There is no clear-cut evidence that the HPC bacteria as a whole pose a public health risk. Only certain members are opportunistic pathogens. Using the four-tiered approach for risk assessment from the National Academy of Sciences, hazard identification, dose-response modeling, and exposure through ingestion of drinking water were evaluated to develop a risk characterization, which estimates the probability of infection for individuals consuming various levels of specific HPC bacteria. HPC bacteria in drinking water often include isolates from the following genera: Pseudomonas, Acinetobacter, Moraxella, Aeromonas, and Xanthomonas. Other bacteria that are commonly found are Legionella and Mycobacterium. All these genera contain species that are opportunistic pathogens which may cause serious diseases. For example, the three nonfermentative gram-negative rods most frequently isolated in the clinical laboratory are (1) Pseudomonas aeruginosa, (2) Acinetobacter, and (3) Xanthomonas maltophilia. P. aeruginosa is a major cause of hospital-acquired infections with a high mortality rate. Aeromonas is sometimes associated with wound infections and suspected to be a causative agent of diarrhea. Legionella pneumophila causes 4%-20% of cases of community-acquired pneumonia and has been ranked as the second or third most frequent cause of pneumonia requiring hospitalization. The number of cases of pulmonary disease associated with Mycobacterium avian is rapidly increasing and is approaching the incidence of M. tuberculosis in some areas. Moraxella can cause infections of the eye and upper respiratory tract. The oral infectious doses are as follows in animal and human test subjects: P. aeruginosa, 10(8)-10(9); A, hydrophila, > 10(10); M. avium, 10(4)-10(7); and X. maltophilia, 10(6)-10(9). The infectious dose for an opportunistic pathogen is lower for immunocompromised subjects or those on antibiotic treatment. These bacteria have been found in drinking water at the following frequencies: P. aeruginosa, < 1%-24%; Acinetobacter, 5%-38%; X. maltophilia, < 1%-2%; Aeromonas, 1%-27%; Moraxella, 10%-80%; M. avium, < 1%-50%; and L. pneumophila, 3%-33%. These data suggest that drinking water could be a source of infection for some of these bacteria. The risk characterization showed that risks of infection from oral ingestion ranged from a low of 7.3 x 10(-9) (7.3/billion) for low exposures to Aeromonas to higher risks predicted at high levels of exposure to Pseudomonas of 9 x 10(-2) (98/100). This higher risk was only predicted for individuals on antibiotics. Overall, the evidence suggests that specific members of HPC bacteria found in drinking water may be causative agents of both hospital- and community-acquired infections. However, the case numbers may be very low and the risks represent levels generally less than 1/10,000 for a single exposure to the bacterial agent. Future research needs include (1) determining the seasonal concentrations of these bacteria in drinking water, (2) conducting adequate dose-response studies in animal subjects or human volunteers, (3) determining the health risks for an individual with multiple exposures to the opportunistic pathogens, and (4) evaluating the increase in host susceptibility conferred by antibiotic use or immunosuppression.

Acinetobacter↗

Research strategies for safety evaluation of nanomaterials, Part III: nanoscale technologies for assessing risk and improving public health.

Risk assessment in the environmental health sciences focuses on understanding the nature of environmental exposures and the potential harm posed by those exposures which in turn is determined by the perturbation of biological pathways and the individual's susceptibility to damage. While there are extensive research efforts ongoing in these areas, progress in each is currently slowed by technological limitations including comprehensive assessment of multiple exposures in real time and dynamic assessment of biological response with high temporal and quantitative resolution. This Forum article discusses recent technological innovations capitalizing on the emergent properties of nanoscale materials and their potential adaptation to improving individual exposure assessment, determination of biological response, and environmental remediation. The ultimate goal is to raise the environmental health science community's awareness of these possibilities and encourage the development of improved strategies for assessing risk and improving public health.

Biomedical Research↗

Exposure to chemicals, physical agents, and biologic agents in mycosis fungoides and the Sézary syndrome.

The history of occupational, environmental, and/or iatrogenic exposure to potential carcinogenic agents was obtained at the time of onset of skin disease in 43 of 44 patients with cutaneous T-cell lymphoma (mycosis fungoides and the Sézary syndrome) entering a National Cancer Institute therapeutic trial. A history of multiple exposures to these agents was common, the two most frequent being chemicals (91% of patients) and drugs (86%). Mean duration of expsosure was 13 years for chemicals and 18 years for drugs. The most common chemicals were air pollutants (39%), pesticides (36%), solvents and vapors (30%), and detergents and disinfectants (14%). Increased severity of disease was seen with increaed duration of chemical exposure in stage V cutaneous T-cell lymphomas only. The most frequent drugs besides tobacco (86%) were analgesics (20%), tranquilizers (18%), and thiazides (14%). Second cancers occurred in four patients, including two renal cell carcinomas, and a family history of cancer was present in 11. Fourteen of 22 patients questioned had recurrent herpes simplex. Patients with chronic skin disease who have long-term exposure to combinations of chemicals, physical agents, and biologic agents, are heavy smokers, or have recurrent herpes simplex appear to be prime candidates for developing mycosis fungoides or the Sézary syndrome.

Adult↗

Microsatellite instability, apoptosis, and loss of p53 function in drug-resistant tumor cells.

We have examined microsatellite instability and loss of p53 function in human tumor cell line models of acquired anticancer drug resistance. We observe acquisition of an RER(+) phenotype in cell lines selected for resistance to cisplatin or doxorubicin. The majority of independent cisplatin-resistant sublines are RER(+), whereas the parental line shows no evidence of microsatellite instability. Microsatellite mutations in random, nonselected subclones of a cislatin-resistant line are observed in the absence of further drug exposure, suggesting that the RER(+) phenotype is a stable phenotype rather than being transiently induced by DNA damage. Furthermore, a cisplatin-resistant derivative shows reduction in a G:T mismatch recognition activity compared to the parental line. Independent lines selected by multiple exposure to cisplatin show resistance factors of up to a 5-fold by clonogenic assay and have reduced cisplatin-induced apoptosis. The resistant lines that are RER(+) show evidence of loss of p53-dependent functions, as measured by a loss of radiation-induced G(1) arrest and reduced CIP1 mRNA. Induced loss of p53 function by transfection of mutant TP53 does not cause a detectable RER(+) phenotype. We speculate that tolerance of DNA damage and expansion of cells with an RER(+) phenotype may select for reduced ability to engage apoptosis and loss of p53 function.

Antibiotics, Antineoplastic↗

Analysis of a historical cohort of Chinese tin miners with arsenic, radon, cigarette smoke, and pipe smoke exposures using the biologically based two-stage clonal expansion model.

Hazelton, W. D., Luebeck, E. G., Heidenreich, W. F. and Moolgavkar, S. H. Analysis of a Historical Cohort of Chinese Tin Miners with Arsenic, Radon, Cigarette Smoke, and Pipe Smoke Exposures Using the Biologically Based Two-Stage Clonal Expansion Model. Radiat. Res. 156, 78-94 (2001).The two-stage clonal expansion model is used to analyze lung cancer mortality in a cohort of Yunnan tin miners based on individual histories with multiple exposures to arsenic, radon, cigarette smoke, and pipe smoke. Advances in methodology include the use of nested dose-response models for the parameters of the two-stage clonal expansion model, calculation of attributable risks for all exposure combinations, use of both a fixed lag and a gamma distribution to represent the time between generation of the first malignant cell and death from lung cancer, and scaling of biological parameters allowed by parameter identifiability. The cohort consists of 12,011 males working for the Yunnan Tin Corporation, with complete exposure records, who were initially surveyed in 1976 and followed through 1988. Tobacco and arsenic dominate the attributable risk for lung cancer. Of 842 lung cancer deaths, 21.4% are attributable to tobacco alone, 19.7% to a combination of tobacco and arsenic, 15.8% to arsenic alone, 11% to a combination of arsenic and radon, 9.2% to a combination of tobacco and radon, 8.7% to combination of arsenic, tobacco and radon, 5.5% to radon alone, and 8.7% to background. The models indicate that arsenic, radon and tobacco increase cell division, death and malignant conversion of initiated cells, but with significant differences in net cell proliferation rates in response to the different exposures. Smoking a bamboo water pipe or a Chinese long-stem pipe appears to confer less risk than cigarette use, given equivalent tobacco consumption.

Adolescent↗