Cancer Related Abstracts
[Genotoxic effect of the insecticides pentachlorophenol and
lindane on human nasal mucosal epithelium].
[Article in German]
Tisch M, Lohmeier A, Schmezer P, Bartsch H, Maier H.
Abteilung fur Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie,
Bundeswehrkrankenhaus Ulm. Matthias.Tisch@extern.uni-ulm.de
BACKGROUND AND OBJECTIVE: In numerous experimental and epidemiologic studies
Pentachlorphenol (PCP) and Hexachlorcyclohexan (Lindane) have been shown to be
of potential carcinogenic risk for human epithelial cells. In the past, these
two substances have been used for both, military and non-military purposes, e.g.
for impregnation of textiles and uniforms. In this study we investigated the
genotoxic effect of PCP and Lindane on human mucosal tissue from the middle and
lower nasal turbinate. METHODS: In biopsy samples obtained from nasal epithelia
during surgery cell vitality was evaluated by trypan-blue-staining. The
specimens were incubated for 60 minutes with PCP (0.3; 0.75 und 1.2 mumol/l) and
Lindane (0.5; 0.75; and 1.0 mumol/ml). The induction of DNA-damage
(single-strand-breaks and double-strand-breaks) caused by PCP and Lindane was
measured using single-cell microgel electrophoresis. Evaluation was performed by
fluorescence microscopy. RESULTS: Especially in mucosa cells from the middle
turbinate severe DNA-damages were recognized after exposition to PCP and Lindane
proposing a strong genotoxic effect. In cells from the lower turbinate
DNA-changes caused by PCP and Lindane were significantly lower. However a
considerable genotoxic effect was also present. CONCLUSION: This study shows for
the first time that there are clear facts indicating mutagenic effects of PCP
and Lindane on nasal epithelia. Furthermore, this is the first study showing
different susceptibility of two anatomic subsites in the nose for different
pesticides. Concerning the biological plausibility, this study offers important
arguments for evaluating the role of PCP and Lindane in the induction of upper
aerodigestive tract cancer.
PMID: 11512281 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/
Upper Aerodigestive Tract Cancer
Dioxin exposure and public health in Chapaevsk, Russia.
Revich B, Aksel E, Ushakova T, Ivanova I, Zhuchenko N, Klyuev N, Brodsky B,
Sotskov Y.
Center for Demography and Human Ecology of Institute for Forecasting, Russian
Academy of Sciences, Moscow, Russian Federation. revich@mail.ecfor.rssi.ru
One of the largest environmental polluters in Chapaevsk (Samara Region, Russia)
is the Middle Volga chemical plant. From 1967 to 1987, it produced
hexachlorocyclohexane (lindane) and its derivatives. Currently, it produces crop
protection chemicals (liquid chlorine acids, methyl chloroform, vinyl chloride,
and some other chemicals). Dioxins were detected in air (0.116 pg/m3), in soil
(8.9-298 ng/kg), in the town's drinking water (28.4-74.1 pg/liter), and in the
cow's milk (the content of 2,3,7,8-TCDD was 17.32 pg TEQ/g fat). The mean
content of dioxins in seven pooled samples of human milk (40 individual trials)
was 42.26 pg TEQ/g fat, in four female workers' blood samples -412.4 pg TEQ/g
fat, in six residents blood samples (those who lived 1-3 km from the chemical
plant) -75.2 pg TEQ/g fat, in four residents' blood samples (5-8 km from the
plant) -24.5 pg TEQ/g fat. To assess cancer risk and reproductive health status,
official medical statistical information was used. In general, the male cancer
mortality observed rate in Chapaevsk is higher than expected. The SMR is higher
for lung cancer 3.1(C.I. 2.6-3.8), urinary organs 2.6(C.I. 1.7-3.6). Chapaevsk
women have a higher risk overall due to breast cancer 2.1(C.I. 1.6-2.7) and
cervix cancer 1.8(C.I. 1.0-3.1). The incidence rates were higher for lung cancer
in males and for female breast cancer in all age groups compared to Russia and
Samara Region in 1998. Significant disruptions in reproductive function were
detected. The mean frequency of spontaneous abortions in the last seven years
was statistically higher 24.4% in Chapaevsk (compared to other of the towns
region). The average rate of premature labor was 45.7 per 1000 women in
Chapaevsk that is significantly higher than in most Samara Region towns. The
frequency of newborns with low birth weight was 7.4%. In Russia and in most of
the Samara Region towns, this rate is lower (6.2-5.1%) but not statistically
different. For the determination of congenital morphogenetic conditions (CMGC),
369 children born between 1990 and 1995 were examined. The average number of
CMGC per child was significantly higher, 4.5 for boys and 4.4 for girls. The
first results indicated serious disruptions associated with high dioxin levels
in human milk and blood in Chapaevsk. We suggest that Chapaevsk is an incredibly
interesting site for further environmental-epidemiological research to assess
the impact of dioxins on human health.
PMID: 11372889 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/
Pesticides and cancer.
Dich J, Zahm SH, Hanberg A, Adami HO.
Department of Cancer Epidemiology, Karolinska Institute and Radiumhemmet,
Karolinska University Hospital, Stockholm, Sweden.
Epidemiologic evidence on the relationship between chemical pesticides and
cancer is reviewed. In animal studies, many pesticides are carcinogenic, (e.g.,
organochlorines, creosote, and sulfallate) while others (notably, the
organochlorines DDT, chlordane, and lindane) are tumor promoters. Some
contaminants in commercial pesticide formulations also may pose a carcinogenic
risk. In humans, arsenic compounds and insecticides used occupationally have
been classified as carcinogens by the International Agency for Research on
Cancer. Human data, however, are limited by the small number of studies that
evaluate individual pesticides. Epidemiologic studies, although sometimes
contradictory, have linked phenoxy acid herbicides or contaminants in them with
soft tissue sarcoma (STS) and malignant lymphoma; organochlorine insecticides
are linked with STS, non-Hodgkin's lymphoma (NHL), leukemia, and, less
consistently, with cancers of the lung and breast; organophosphorous compounds
are linked with NHL and leukemia; and triazine herbicides with ovarian cancer.
Few, if any, of these associations can be considered established and causal.
Hence, further epidemiologic studies are needed with detailed exposure
assessment for individual pesticides, taking into consideration work practices,
use of protective equipment, and other measures to reduce risk.
Publication Types:
PMID: 9498903 [PubMed - indexed for MEDLINE
|
Walsh LP, Stocco DM |
|
Effects of lindane on steroidogenesis and steroidogenic acute regulatory
protein expression.
|
|
Biol Reprod; 63(4):1024-33 2000 UI: 20450785
|
| ABSTRACT:
Lindane, the gamma isomer of hexachlorocyclohexane (HCH), is one of the
oldest synthetic pesticides still in use worldwide. Numerous reports have shown
that this pesticide adversely affects reproductive function in animals. Although
the pathogenesis of reproductive dysfunction is not yet fully understood, recent
reports indicate that lindane can directly inhibit adrenal and gonadal
steroidogenesis. Because Leydig cells play a pivotal role in male reproductive
function through the production of testosterone, the mouse MA-10 Leydig tumor
cell line was used to assess the potential effects of gamma-HCH and its isomers,
alpha-HCH and delta-HCH, on steroid production, steroidogenic enzyme expression
and activity, and steroidogenic acute regulatory (StAR) protein expression. StAR
mediates the rate-limiting and acutely regulated step in hormone-stimulated
steroidogenesis, the intramitochondrial transfer of cholesterol to the P450(scc)
enzyme. Our studies demonstrate that alpha-, delta-, and gamma-HCH inhibited
dibutyryl ([Bu](2)) cAMP-stimulated progesterone production in MA-10 cells in a
dosage-dependent manner without affecting general protein synthesis; and protein
kinase A or steroidogenic enzyme expression, activity, or both. In contrast,
each of these isomers dramatically reduced (Bu)(2)cAMP-stimulated StAR protein
levels. Therefore, our results are consistent with the hypothesis that alpha-,
delta-, and gamma-HCH inhibited steroidogenesis by reducing StAR protein
expression, an action that may contribute to the pathogenesis of lindane-induced
reproductive dysfunction.
|
Abstract of Meeting Paper
Society for Risk Analysis 1998
Annual Meeting
Re-Evaluation of the Potential Carcinogenicity of Lindane.
P. C. Chrostowski and G. Charnley, The Weinberg Group Inc., Washington, DC
The benzene hexachloride (BHC) isomers have been widely used as pesticides
since the 1930s. One of the isomers, gamma-BHC or lindane is currently
registered as an insecticide and approved by the Food and Drug Administration
(FDA) for topical use to control lice in humans. In addition, due to their
widespread use and relative persistence in groundwater, the BHCs have been
designated as chemicals of potential concern at numerous Superfund sites. In the
late 1970s the Environmental Protection Agency (EPA) conducted chemical-specific
risk assessments of the BHCs including lindane and determined, on the basis of
rodent feeding studies, that these chemicals were either possible or probable
human carcinogens. EPA also published cancer slope factors for three of the
isomers based on application of the linearized multistage model to the rodent
bioassay data. EPA is currently re-evaluating the Integrated Risk Information
System (IRIS) entries for the BHCs. In parallel with EPA’s activity, we are
re-evaluating the potential carcinogenicity and systemic toxicity of these
compounds. This paper will present the initial findings of our evaluation
including a review of data adequacy, analysis of toxicological mechanism of
action, and a re-assessment of the chemical carcinogenicity using EPA’s newly
developed cancer guidelines.
Doherty AT, Ellard S, Parry EM, Parry JM
An investigation into the activation and deactivation of chlorinated
hydrocarbons to genotoxins in metabolically competent human cells.
Mutagenesis; 11(3):247-74 1996 UI: 96325151
We have investigated the induction of micronuclei by 15 chlorinated
hydrocarbons in the cytochalasin B-blocked micronucleus assay utilizing
genetically engineered cell lines. The human lymphoblastoid cell line AHH-1,
with native cytochrome CYP1A1 activity, the MCL-5 cell line, which stably
expresses cDNAs encoding human CYP1A2, 2A6, 3A4, 2E1 and microsomal epoxide
hydrolase, and the h2E1 cell line, containing a cDNA for CYP2E1, were used in
this study. We have demonstrated the induction of kinetochore-positive
micronuclei by two chlorinated solvents, 2,3-dichlorobutane and 1,1,
2-trichloroethane, in the metabolically competent cell lines MCL-5 and h2E1. The
MCL-5 and h2E1 cell lines have in addition shown the capacity to produce
metabolites in the presence of methylene chloride, carbon tetrachloride,
1,2,3-trichloropropane, tetrachloroethylene, toluene and n-hexane, wich yield
elevated micronucleus frequencies compared with the parental cell line AHH-1.
Hexachloroethane failed to induce micronuclei in any of the cell lines and
1,2-dichloroethane and 1-chlorohexane induced micronuclei without the
requirement for metabolic activation in all three cell lines. The MCL-5 cell
line exhibited reduced micronucleus frequencies compared with the AHH-1 and h2E1
cell lines following exposure to 1,2-dichloroethylene, 1,3-dichloropropane, 1,1,
1-trichloroethane and 1,2,3-trichloropropane. The methodology used has shown the
ability of metabolically competent cell lines expressing cDNAs encoding the
cytochrome P450 isoenzymes to metabolize halogenated hydrocarbons to genotoxic
species, including both clastogens and aneugens. The biotransformation of
chemicals to aneugenic species has not previously been demonstrated.
B-Lymphocytes/Ultrastructure
Cytochrome P-450/Drug Effects/Genetics/Metabolism
Dose-Response Relationship, Drug
Fluorescent Antibody Technique, Indirect
Human
Hydrocarbons/*Metabolism/*Toxicity
Micronucleus Tests
Mutagens/Toxicity
Support, Non-U.S. Gov't
Tumor Cells, Cultured
ENG
JOURNAL ARTICLE
Mutagenesis
1996
School of Biological Sciences, University of Wales, Singleton Park, Swansea SA2
8PP, UK.
199612
0 (Hydrocarbons),0 (Mutagens),,9035-51-2 (Cytochrome P-450)
Moser GJ Smart RC
Hepatic tumor-promoting chlorinated hydrocarbons stimulate protein kinase C
activity.
In: Carcinogenesis (1989 May) 10(5):851-6
Various chlorinated hydrocarbons, many of which are known hepatic tumor
promoters, have been evaluated for their ability to stimulate protein kinase C (PKC)
activity in vitro. Chlordane, kepone, toxaphene, heptachlor,
2,2-bis(4-chlorophenyl)-1,1-dichloroethane, the polychlorinated biphenyl Aroclor
1254, aldrin, 2,2-bis(4- chlorophenyl)-1,1,1-trichloroethane (DDT) and gamma-
hexachlorocyclohexane (lindane) were the most potent stimulators of PKC
activity. Of these compounds, chlordane was the most potent organochlorine
pesticide. Chlordane (100 microM) stimulated mouse brain PKC activity in the
10(5) g supernatant to a maximum velocity equal to that obtained when the enzyme
was maximally stimulated with the skin-tumor-promoting phorbol ester,
12-O-tetradecanoylphorbol-13- acetate (TPA). Chlordane concentrations as low as
1 microM significantly stimulated PKC activity. Chlordane-stimulated PKC
activity was calcium-dependent, and in the presence of exogenous calcium,
chlordane-stimulated PKC activity was at least 5-fold greater than in the
absence of added calcium. In contrast, the addition of calcium only minimally
affected (less than 30% increase) the TPA-stimulated PKC activity.
Concentrations of TPA and chlordane which maximally stimulate PKC did not
produce an additive effect on PKC activity. Chlordane- and TPA- stimulated PKC
activity was phospholipid-dependent and could be inhibited by quercetin, a known
inhibitor of PKC activity. Chlordane in the presence of calcium also stimulated
mouse epidermal and hepatic PKC as well as purified rat brain PKC. These results
demonstrate that a wide variety of chlorinated hydrocarbons, which are
considered hepatic tumor promoters, stimulate protein kinase C activity in
vitro.
Institutional address:
Toxicology Program
North Carolina State University
Raleigh 27695-7633.
|
LINDANE: Questions and Answers
Q. What is lindane?
A. Lindane (hexachlorocyclohexane) is a man-made organochlorine pesticide
used for agricultural purposes and as a widely prescribed topical treatment for
lice and scabies. Previously marketed under the brandname, Kwell®, lindane is
available in generic form, as well as the brand name products including:
Bio-Well, GBH, G-well, Kildane, Kwildane, Scabene, and Thionex. Lindane is a
prescription strength medication, available in lotion (1% lindane), cream (1%)
and shampoo (1 %).
Q. Does lindane cause cancer?
A. Lindane has been shown to be a human carcinogen. Recent case control
studies report high rates of childhood brain cancer treated with lindane
shampoo.1 These findings are supported by several reports of six-fold
increases non-Hodgkin's lymphoma in farmers exposed to lindane,2
Evidence of carcinogenicity is confirmed by the World Health Organization,
the Environmental Protection Agency and the Department of Health and Human
Services.
Q. Does lindane cause any other health problems?
A. Lindane is known hemotoxin-blood poison. In many case
reports, lindane exposure from recommended dosages has resulted in blood
diseases such as aplastic anemia.3 Aplastic anemia, which has a high
fatality rate, is a precursor to leukemia.
Lindane is also a neurotoxin - nerve poison. In many cases,
treatment with lindane shampoos have resulted in vomiting, seizures, brain
damage, and comas, Adverse effects have resulted from recommended dosages of
this product.4
Q. Who is most at risk from exposure to lindane?
A. Children under the age of seven, children who were born
premature, and pregnant women are the most at risk for immediate adverse effects
from lindane exposure. Lindane is readily absorbed through the skin and can
immediately cause central nervous system damage. It has also been shown to pass
through the placenta, creating a serious risk for expectant mothers.
Absorption of lindane is increased when applied with warm water
or followed by oil-based hair care products
Q. Is lindane regulated by the government?
A. The Food and Drug Administration (FDA) regulates all
pharmaceutical products, lindane included. To date, the FDA has taken very
little action to inform patients of the long term effects of exposure to lindane.
The Environmental Protection Agency has severly restricted the use of lindane as
an agricultural pesticide due to lindane's adverse health effects.
|
Cancer Prevention Coalition c/o School of Public Health
|
|
University of Illinois Medical Center
|
|
2121 West Taylor Street
|
|
Chicago, IL 60612
|
|
Tel: (312) 996-2297, Fax: (312) 996-1374
|
|
Email: epstein@uic.edu
|
Reference:
|
|
1. Davis JR, Brownson RC, Garcia R, Beniz BJ and Turner A. "Family
pesticide use and childhood brain cancer." Arch Environ Contam Toxicol
24: 87-92, 1993.
2. Cantor KP, Blair A, Everett G, Gibson R, Burmeister LF, Brown LM, Schuman
L and Dick FR. "Pesticides and other agricultural risk factors for
non-Hodgkin's lyrnphoma among men in Iowa and Minnesota," Cancer Res.
52: 2447-2455, 1992.
3. Agency for Toxic Substances and Disease Registry. "Toxicological
profile for alpha-, beta- gamma-, and delt-hexachlorocyclohexane (update)."
U.S. Department of Health and Human Services, Pub. No. TP-93.09, May 1994.
4. Solomon LM, west DP and Fitzloff JF. " Lindane." Letter, Arch
Dermatol 126: 248, 1990.
|
Cancer
|