tumor promotion with sodium bicarbonate

[Guest guest]

List, The following abstracts speak to the probable inadvisability

of inducing extremes of pH. Sodium bicarbonate (NaHCO3) is used in

animal models as a tumor promoter. Table salt (NaCl) can be equally troubling.

----------------------------------------------

Food Chem Toxicol. 1999 Dec;37(12):1159-66.

Effect of urinary pH on the progression of urinary bladder tumours.

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Lina%20BA\

%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Di\

scoveryPanel.Pubmed_RVAbstractPlus>Lina

BA,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22van%20Gar\

deren-Hoetmer%20A%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_Resul\

tsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus>van

Garderen-Hoetmer A.

TNO Nutrition and Food Research Institute, AJ, Zeist, The Netherlands.

Systemic alkalosis has been postulated to enhance tumorigenesis,

whereas systemic acidosis has been implicated to exert a favourable

influence on tumour control and regression. In the present study the

urinary pH was influenced by feeding acid-forming or base-forming

diets, and the effect of alkaline or acid urine on the early and late

progression phase of urinary bladder carcinogenicity was investigated

in male Wistar rats. Bladder lesions were initiated by

N-butyl-N-(4-hydroxybutyl) nitrosamine (0.05% BBN in the drinking

water during 4 weeks) and promoted by sodium bicarbonate (3.4% NaHCO3

in the diet during 15 or 25 weeks). After short- (15 week) and more

long-term (25 week) promotion with NaHCO3, groups of 20 rats were fed

a diet containing the acidifying salt ammonium chloride (2.1% NH4Cl)

or the control diet. All surviving rats were killed after a total

study duration of 52 weeks. Additional control groups were, after

initiation, fed diets containing NaHCO3 and killed after 15 wk or 25

wk of promotion, or at the end of the study. In rats fed diets with

added salts, water intake and the amount of urine produced were

increased and the urinary density was decreased compared to rats fed

control diet. During NaHCO3 feeding, urinary pH and sodium

concentration were increased. During NH4Cl feeding, urinary pH was

decreased and urinary chloride and calcium concentrations were

increased. Initiation by BBN followed by treatment with NaHCO3 caused

a high incidence of papillary/nodular hyperplasia, papillomas and

carcinomas of the bladder epithelium. These lesions progressed with

time or longer duration of NaHCO3 promotion. A tumour protective

effect of urinary acidification by NH4Cl was not found. In fact, both

acidification and prolonged alkalinization tended to aggravate the

malignancy of bladder carcinomas.

PMID: 10654592 [PubMed - indexed for MEDLINE]

-------------------------------------

Food Chem Toxicol. 2004 Jan;42(1):135-53.

Toxicity and carcinogenicity of acidogenic or alkalogenic diets in

rats; effects of feeding NH(4)Cl, KHCO(3) or KCl.

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Lina%20BA\

%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Di\

scoveryPanel.Pubmed_RVAbstractPlus>Lina

BA,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Kuijpers%\

20MH%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_DiscoveryPanel.Pubmed_RVAbstractPlus>Kuijpers

MH.

TNO Nutrition and Food Research, PO Box 360, 3700 AJ The, Zeist,

Netherlands. lina@...

The effects of diet-induced acid-base disturbances were examined in

4-week, 13-week and 18-month toxicity studies, and in a 30-month

carcinogenicity study. Rats were fed a natural ingredient diet

(controls), supplemented with 2% or 4% KHCO(3) (base-forming diets),

or with 1% or 2.1% NH(4)Cl (acid-forming diets). Additional controls

were fed 3% KCl (neutral diet providing K(+) and Cl(-) in amounts

equimolar to those in the 4% KHCO(3) diet and the 2.1% NH(4)Cl diet,

respectively). NH(4)Cl induced the expected metabolic acidosis, as

shown by decreased base excess in blood, decreased urinary pH and

increased urinary net acid excretion. KHCO(3) induced the opposite

effects. KCl did not affect the acid-base balance. Clinical condition

and death rate were not affected. The feeding of high levels of each

salt resulted in growth retardation and increased water intake and

urinary volume. Plasma potassium and urinary potassium excretion were

increased with KHCO(3) and KCl. Plasma chloride was increased with

NH(4)Cl, but not with KCl. Urinary calcium and phosphate excretion

were increased with NH(4)Cl, but there were no indications that bone

minerals were involved (weight, calcium content and fat free solid of

the femur were not affected). Standard haematological and clinical

chemistry parameters were not affected. Kidney weights were increased

with 2.1% NH(4)Cl. Hypertrophy of the adrenal zona glomerulosa

occurred with KHCO(3), KCl and NH(4)Cl, due to chronic stimulation of

the adrenal cortex by either K(+) or by NH(4)Cl-induced acidosis. An

early onset (from week 13) of oncocytic tubules was noted in the

kidneys of rats fed KHCO(3) and, after 30 months, the incidence of

this lesion was much higher than the background incidence in ageing

controls. No progression to oncocytomas was noted. KCl showed only

slight effects on the early onset of oncocytic tubules (from 18

months). In contrast, the severity of nephrosis and the incidence of

oncocytic tubules were decreased with 2.1% NH(4)Cl, suggesting a

protective effect of acidosis. The feeding of KHCO(3) resulted in

hyperplasia, papillomas and carcinomas of the urinary bladder. With

KCl only a slight increase in proliferative urothelial lesions was

noted. Apart from these (pre-)neoplastic lesions in the urinary

bladder there were no treatment-related differences in tumour

response among the groups. We concluded that most of the observed

changes represent physiological adaptations to the feeding of acid-

or base-forming salts. Remarkable effects noted with KHCO(3), and to

a far lesser extent with KCl, consisted of renal oncocytic tubules

and (pre-)neoplastic lesions of the urinary bladder epithelium.

NH(4)Cl-induced chronic metabolic acidosis was not associated with

dissolution of alkaline bone salts in rats. Finally, a protective

effect of chronic acidosis on tumour development was not found.

PMID: 14630137 [PubMed - indexed for MEDLINE]

----------------------------------

Eur J Nutr. 2001 Oct;40(5):200-13.

Diet, evolution and aging--the pathophysiologic effects of the

post-agricultural inversion of the potassium-to-sodium and

base-to-chloride ratios in the human diet.

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Frassetto\

%20L%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_DiscoveryPanel.Pubmed_RVAbstractPlus>Frassetto

L,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22%20\

RC%20Jr%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pu\

bmed_DiscoveryPanel.Pubmed_RVAbstractPlus>

RC Jr,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Sellmeyer\

%20DE%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubm\

ed_DiscoveryPanel.Pubmed_RVAbstractPlus>Sellmeyer

DE,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Todd%20K%\

22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Dis\

coveryPanel.Pubmed_RVAbstractPlus>Todd

K,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Sebastian\

%20A%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_DiscoveryPanel.Pubmed_RVAbstractPlus>Sebastian

A.

University of California, San Francisco 94143, USA.

Theoretically, we humans should be better adapted physiologically to

the diet our ancestors were exposed to during millions of years of

hominid evolution than to the diet we have been eating since the

agricultural revolution a mere 10,000 years ago, and since

industrialization only 200 years ago. Among the many health problems

resulting from this mismatch between our genetically determined

nutritional requirements and our current diet, some might be a

consequence in part of the deficiency of potassium alkali salts

(K-base), which are amply present in the plant foods that our

ancestors ate in abundance, and the exchange of those salts for

sodium chloride (NaCl), which has been incorporated copiously into

the contemporary diet, which at the same time is meager in

K-base-rich plant foods. Deficiency of K-base in the diet increases

the net systemic acid load imposed by the diet. We know that

clinically-recognized chronic metabolic acidosis has deleterious

effects on the body, including growth retardation in children,

decreased muscle and bone mass in adults, and kidney stone formation,

and that correction of acidosis can ameliorate those conditions. Is

it possible that a lifetime of eating diets that deliver

evolutionarily superphysiologic loads of acid to the body contribute

to the decrease in bone and muscle mass, and growth hormone

secretion, which occur normally with age? That is, are contemporary

humans suffering from the consequences of chronic, diet-induced

low-grade systemic metabolic acidosis? Our group has shown that

contemporary net acid-producing diets do indeed characteristically

produce a low-grade systemic metabolic acidosis in otherwise healthy

adult subjects, and that the degree of acidosis increases with age,

in relation to the normally occurring age-related decline in renal

functional capacity. We also found that neutralization of the diet

net acid load with dietary supplements of potassium bicarbonate

(KHCO3) improved calcium and phosphorus balances, reduced bone

resorption rates, improved nitrogen balance, and mitigated the

normally occurring age-related decline in growth hormone

secretion--all without restricting dietary NaCl. Moreover, we found

that co-administration of an alkalinizing salt of potassium

(potassium citrate) with NaCl prevented NaCl from increasing urinary

calcium excretion and bone resorption, as occurred with NaCl

administration alone. Earlier studies estimated dietary acid load

from the amount of animal protein in the diet, inasmuch as protein

metabolism yields sulfuric acid as an end-product. In cross-cultural

epidemiologic studies, Abelow found that hip fracture incidence in

older women correlated with animal protein intake, and they suggested

a causal relation to the acid load from protein. Those studies did

not consider the effect of potential sources of base in the diet. We

considered that estimating the net acid load of the diet (i. e., acid

minus base) would require considering also the intake of plant foods,

many of which are rich sources of K-base, or more precisely base

precursors, substances like organic anions that the body metabolizes

to bicarbonate. In following up the findings of Abelow et al., we

found that plant food intake tended to be protective against hip

fracture, and that hip fracture incidence among countries correlated

inversely with the ratio of plant-to-animal food intake. These

findings were confirmed in a more homogeneous population of white

elderly women residents of the U.S. These findings support

affirmative answers to the questions we asked above. Can we provide

dietary guidelines for controlling dietary net acid loads to minimize

or eliminate diet-induced and age-amplified chronic low-grade

metabolic acidosis and its pathophysiological sequelae. We discuss

the use of algorithms to predict the diet net acid and provide

nutritionists and clinicians with relatively simple and reliable

methods for determining and controlling the net acid load of the

diet. A more difficult question is what level of acidosis is

acceptable. We argue that any level of acidosis may be unacceptable

from an evolutionarily perspective, and indeed, that a low-grade

metabolic alkalosis may be the optimal acid-base state for humans.

PMID: 11842945 [PubMed - indexed for MEDLINE]

----------------------------

Am J Physiol Renal Physiol. 2007 Aug;293(2):F521-5. Epub 2007 May 23.

Dietary sodium chloride intake independently predicts the degree of

hyperchloremic metabolic acidosis in healthy humans consuming a net

acid-producing diet.

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Frassetto\

%20LA%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubm\

ed_DiscoveryPanel.Pubmed_RVAbstractPlus>Frassetto

LA,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22%20\

RC%20Jr%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pu\

bmed_DiscoveryPanel.Pubmed_RVAbstractPlus>

RC Jr,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Sebastian\

%20A%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_DiscoveryPanel.Pubmed_RVAbstractPlus>Sebastian

A.

Dept. of Medicine and General Clinical Research Center, University of

California, San Francisco, CA 94143, USA. frassett@...

We previously demonstrated that typical American net acid-producing

diets predict a low-grade metabolic acidosis of severity proportional

to the diet net acid load as indexed by the steady-state renal net

acid excretion rate (NAE). We now investigate whether a sodium (Na)

chloride (Cl) containing diet likewise associates with a low-grade

metabolic acidosis of severity proportional to the sodium chloride

content of the diet as indexed by the steady-state Na and Cl

excretion rates. In the steady-state preintervention periods of our

previously reported studies comprising 77 healthy subjects, we

averaged in each subject three to six values of blood hydrogen ion

concentration ([H], plasma bicarbonate concentration

([HCO(3)(-)]p), the partial pressure of carbon dioxide (Pco(2)), the

urinary excretion rates of Na, Cl, NAE, and renal function as

measured by creatinine clearance (CrCl), and performed multivariate

analyses. Dietary Cl strongly correlated positively with dietary Na

(P < 0.001) and was an independent negative predictor of [HCO(3)(-)]p

after adjustment for diet net acid load, Pco(2) and CrCl, and

positive and negative predictors, respectively, of [H]b and

[HCO(3)(-)]p after adjustment for diet acid load and Pco(2). These

data provide the first evidence that, in healthy humans, the diet

loads of NaCl and net acid independently predict systemic acid-base

status, with increasing degrees of low-grade hyperchloremic metabolic

acidosis as the loads increase. Assuming a causal relationship, over

their respective ranges of variation, NaCl has approximately 50-100%

of the acidosis-producing effect of the diet net acid load.

PMID: 17522265 [PubMed - indexed for MEDLINE]

-----------------------

Kidney Int. 1987 Jun;31(6):1356-67.

Dietary NaCl determines severity of potassium depletion-induced

metabolic alkalosis.

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22\

%20RE%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubm\

ed_DiscoveryPanel.Pubmed_RVAbstractPlus>

RE,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Schambela\

n%20M%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubm\

ed_DiscoveryPanel.Pubmed_RVAbstractPlus>Schambelan

M,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Cogan%20M\

G%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_D\

iscoveryPanel.Pubmed_RVAbstractPlus>Cogan

MG,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Colman%20\

J%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_D\

iscoveryPanel.Pubmed_RVAbstractPlus>Colman

J,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22%20\

RC%20Jr%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pu\

bmed_DiscoveryPanel.Pubmed_RVAbstractPlus>

RC Jr,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Sebastian\

%20A%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_DiscoveryPanel.Pubmed_RVAbstractPlus>Sebastian

A.

It is uncertain whether, in humans, potassium depletion can cause or

sustain metabolic alkalosis of clinically important degree in the

absence of coexisting known alkalosis-producing conditions.

Previously we found, in normal humans ingesting abundant NaCl, that

dietary K+ depletion alone can induce and sustain a small decrease in

blood acidity and increase in plasma bicarbonate concentration; we

hypothesized that more severe alkalosis was prevented by mitigating

mechanisms initiated by renal retention of dietary NaCl that was

induced by K+ depletion. To ascertain the acid-base response to

dietary K+ depletion under conditions in which the availability of

NaCl for retention is greatly limited, in the present study of six

normal men we restricted dietary K+ as in the previous study except

that intake of NaCl was maintained low (2 to 7 mEq/day, Low NaCl

Group) instead of high (126 mEq/day, High NaCl Group). Plasma

acid-base composition and renal net-acid excretion (NAE) did not

differ significantly between groups during the control period. In the

steady state of K+ depletion (days 11 to 15 of K+ restriction),

neither plasma K+ concentration (2.9 +/- 0.9 mEq/liter vs. 3.0 +/-

0.1 mEq/liter) nor cumulative K+ deficit (399 +/- 59 mEq vs. 466 +/-

48 mEq) differed significantly between groups. During K+ restriction,

persisting metabolic alkalosis developed in both groups, which was

more severe in the Low NaCl Group: increment in [HCO3-]p, 7.5 +/- 1.0

mEq/liter versus 2.0 +/- 0.3 mEq/liter, P less than 0.001; decrement

in [H+]p, 5.5 +/- 0.6 nEq/liter versus 2.9 +/- 0.4 nEq/liter, P less

than 0.003. A significantly more severe alkalosis in the Low NaCl

Group was evident at all degrees of K+ deficiency achieved during the

course of the 15 days of K+ restriction, and the severity of

alkalosis in the Low NaCl Group correlated with the degree of K+

deficiency. During the generation of alkalosis (days 1 to 7 of K+

restriction), NAE increased in the Low NaCl Group whereas it

decreased in the High NaCl Group. During the maintenance of alkalosis

(days 11 to 15), NAE stabilized in both groups after it returned to

values approximating the control values. In both groups, urine Cl-

excretion decreased during K+ restriction even though Cl- intake had

not been changed, with the result that body Cl- content increased

negligibly in the Low NaCl Group (28 +/- 6 mEq) and substantially in

the High NaCl Group (355 +/- 64 mEq).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID: 3039234 [PubMed - indexed for MEDLINE]

-------------------------

Toxicol Pathol. 1997 May-Jun;25(3):284-90.

Dose-dependent amplification by L-ascorbic acid of NaHCO3 promotion

of rat urinary bladder carcinogenesis.

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Iwata%20H\

%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Di\

scoveryPanel.Pubmed_RVAbstractPlus>Iwata

H,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Yamamoto%\

20S%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\

_DiscoveryPanel.Pubmed_RVAbstractPlus>Yamamoto

S,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Yano%20Y%\

22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Dis\

coveryPanel.Pubmed_RVAbstractPlus>Yano

Y,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Ohtani%20\

S%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_D\

iscoveryPanel.Pubmed_RVAbstractPlus>Ohtani

S,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Fukushima\

%20S%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_DiscoveryPanel.Pubmed_RVAbstractPlus>Fukushima

S.

First Department of Pathology, Osaka City University Medical School, Japan.

The dose dependence of L-ascorbic acid (AsA) copromotion of urinary

bladder carcinogenesis with continuous concomitant administration of

NaHCO3 was investigated. In the first experiment, 83 male F344 rats

were all given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for

4 wk and then divided into 5 groups, which received basal diet

(Oriental MF) containing AsA at 0, 1, 2, 3.5, or 5% plus 1.5% NaHCO3

for 32 wk. Relative urinary bladder weights in the 5% AsA group were

significantly increased as compared to the 0 or 1% group values due

to the development of tumors. Both the incidence and number of

microscopic urinary bladder lesions (tumors and preneoplastic

lesions) showed dose-dependent increases. Furthermore, the sizes of

the urinary bladder tumors (carcinomas and papillomas) were

significantly increased with the highest dose,

5-bromo-2'-deoxyuridine labeling indices showed slightly increased

proliferation in preneoplastic lesions of the urinary bladder

epithelium with 5% AsA treatment. In a separate experiment, scanning

electron microscopic observation revealed that administration of 5%

AsA plus 1.5% NaHCO3 for 8 wk, without BBN, altered the urinary

bladder surface. Elevation of urinary bladder epithelium AsA content,

as well as urinary AsA, was also noted. Ornithine decarboxylase (ODC)

activity and ODC messenger RNA levels in urinary bladder epithelium

of rats treated with 1.5% NaHCO3 plus 5% AsA for 8 wk showed no

statistically significant differences as compared to the control

group. The results indicate that AsA amplifies the rat urinary

bladder carcinogenesis promotion activity of NaHCO3 and that its

intensity of action depends on the dose, particularly at high dose.

PMID: 9210260 [PubMed - indexed for MEDLINE]

-------------------------------

Carcinogenesis. 1988 Jul;9(7):1203-6.

The role of urinary pH and sodium ion concentration in the promotion

stage of two-stage carcinogenesis of the rat urinary bladder.

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Fukushima\

%20S%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_DiscoveryPanel.Pubmed_RVAbstractPlus>Fukushima

S,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Tamano%20\

S%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_D\

iscoveryPanel.Pubmed_RVAbstractPlus>Tamano

S,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Shibata%2\

0MA%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\

_DiscoveryPanel.Pubmed_RVAbstractPlus>Shibata

MA,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Kurata%20\

Y%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_D\

iscoveryPanel.Pubmed_RVAbstractPlus>Kurata

Y,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Hirose%20\

M%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_D\

iscoveryPanel.Pubmed_RVAbstractPlus>Hirose

M,

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Ito%20N%2\

2%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Disc\

overyPanel.Pubmed_RVAbstractPlus>Ito

N.

First Department of Pathology, Nagoya City University Medical School, Japan.

The promoting activities of NaHCO3 and NaCl in two-stage urinary

bladder carcinogenesis in rats initiated with

N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated. Male

F344 rats were given 0.05% BBN in their drinking water for 4 weeks

and then treated with basal diet containing either 3% NaHCO3, 1% NaCl

or no added chemical for 32 weeks. NaHCO3 significantly increased the

induction of neoplastic and preneoplastic lesions of the urinary

bladder, whereas NaCl did not. NaHCO3 produced elevation of urinary

pH and urinary Na+ concentration. NaCl increased urinary Na+

concentration without the elevation of urinary pH. In an additional

experiment, DNA synthesis in the urinary bladder epithelium was

significantly increased in the groups given 3% NaHCO3, 5% sodium

L-ascorbate and 1% NaCl. These results confirm that urinary

components, increase in urinary pH and Na+ concentration play an

important role in the promotion of urinary bladder carcinogenesis in rats.

PMID: 2838196 [PubMed - indexed for MEDLINE]